Study of Lenvatinib in Children and Adolescents With Refr... | NCT02432274

NCT02432274

ID	Type	Description	Link
2013-005534-38	EudraCT Number

Status Module

Sponsor/Collaborators Module

Name	Class
Merck Sharp & Dohme LLC	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort 1: Single-Agent Dose-Finding	Experimental	Children and adolescents with relapsed or refractory solid malignant tumors.	Drug: Lenvatinib
Cohort 2A: Single-agent Expansion (DTC)	Experimental	Children and adolescents with 131 iodine-refractory DTC.	Drug: Lenvatinib
Cohort 2B: Single-agent Expansion (Osteosarcoma)	Experimental	Participants with relapsed or refractory osteosarcoma.	Drug: Lenvatinib
Cohort 3A: Combination Dose-finding	Experimental	Participants with relapsed or refractory osteosarcoma will receive lenvatinib in combination with ifosfamide and etoposide.	Drug: Lenvatinib Drug: Ifosfamide Drug: Etoposide
Cohort 3B: Combination Expansion	Experimental	Participants with relapsed or refractory osteosarcoma will receive lenvatinib in combination with ifosfamide and etoposide.	Drug: Lenvatinib Drug: Ifosfamide Drug: Etoposide

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Lenvatinib	Drug	Cohort 1: Lenvatinib will be administered orally, once daily on Days 1 to 28 of each 28-day cycle at a starting dose of 11 mg/m2. Dose can be de-escalated to 9 mg/m2 or escalated to 14 and 17 mg/m2.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Cohort 1: Recommended Dose (RD) of Lenvatinib	RD was defined as the dose that had a dose limiting toxicity (DLT) rate closest to the targeted 20% rate. DLT was an adverse drug reaction and was assessed according to common terminology criteria for adverse events (CTCAE) version (v) 4.03 defined as 1) Grade 4 neutropenia for greater than or equal to (>=) 7 days, 2) Grade >=3 thrombocytopenia with bleeding, or lasting greater than (>) 7 days, 3) Grade >=3 febrile neutropenia, 4) Next course of chemotherapy delayed for >=7 days, 5) Grade >=3 non-hematologic toxicity persisting >7 days optimal supportive care, 6) Grade 4 hypertension, confirmed systolic or diastolic blood pressure >25 millimeters of mercury (mmHg) above the 95th percentile for age, or an elevated diastolic blood pressure (that is, >95th percentile for age) not controlled by a single antihypertensive medication within 14 days of use, 7) Grade 3 proteinuria, 8) Any recurrent Grade 2 non-hematological toxicity requiring >=2 interruption and dose reductions.	Cycle 1 (28 days)
Cohort 2A: Number of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR)	OR was defined as participants with best overall response (BOR) of CR or PR as assessed by investigator based on response evaluation criteria in solid tumors (RECIST) version (v) 1.1. For OR, the BOR was defined as the best response (CR or PR for >4 weeks) recorded from the start of the treatment until PD or death whichever occurred first. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.	From date of first dose of study drug until first documentation of PD or death, whichever occurred first (until the data cut-off date, 31 May 2019)
Cohort 2A: Number of Participants With Best Overall Response (BOR)

Secondary Outcomes

Measure	Description	Time Frame
Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR)	BOR: best response of CR or PR for >4 weeks or SD for >=7 weeks from first dose, recorded from start of treatment until PD or death, whichever occurred first based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have reduction in their short axis <10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Not evaluable (NE) means BOR of NE or SD of <7 weeks duration. Unknown means no data were available on the case report form.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically or cytologically confirmed diagnosis of solid malignant tumor.
1. Cohort 1: Any solid malignant tumor.
2. Cohort 2A: Differentiated Thyroid Cancer (DTC) with one of the following histological subtypes:
i) Papillary thyroid cancer (PTC). i.a) Follicular variant. i.b) Other variants (including but not limited to tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin's-like, trabecular, tumor with nodular fasciitis-like stroma, Hurthle cell variant of papillary carcinoma, or poorly differentiated carcinomas).

ii) Follicular thyroid cancer (FTC). ii.a) Hurthle cell. ii.b) Clear cell. ii.c) Insular.

c) Cohort 2B, 3A, and 3B: Relapsed or refractory osteosarcoma.
Relapsed or refractory solid tumor malignancy that has progressed on standard anticancer therapy with no available curative options. (Note: Osteosarcoma participants must be in first or subsequent relapse [greater than or equal to first relapse]). Only the osteosarcoma participants enrolled to Cohorts 3A and 3B must be deemed candidates for ifosfamide and etoposide chemotherapy).
Evaluable or measurable disease that meets the following criteria:
1. Participants must have evaluable or measurable disease based on RECIST 1.1 using computed tomography (CT)/magnetic resonance imaging (MRI).
2. Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must have subsequently grown unequivocally to be deemed a target lesion.
DTC participants must be 131 iodine-refractory/ relapsed as defined by at least one of the following:
1. One or more evaluable or measurable lesions that do not demonstrate iodine uptake on any radioiodine scan; or
2. One or more evaluable or measurable lesions that have progressed based on RECIST 1.1, within 12 months of 131 iodine therapy, despite demonstration of radioiodine avidity at the time of that treatment by pre- or post-treatment scanning. These participants must not be eligible for possible curative surgery; or
3. Cumulative activity of 131 iodine greater than 400 millicuries (mCi) or 14.8 gigabecquerels (GBq), with the last dose administered at least 6 months prior to study entry.
Participants with DTC must be receiving thyroxine suppression therapy and levels of thyroid stimulating hormone (TSH) should not be elevated (TSH should be less than or equal to 5.50 milliunits per liter (mU/L)). When tolerated by the participant, thyroxine dose should be changed to achieve TSH suppression (TSH less than 0.50 mU/L).
Participants with known central nervous system (CNS) primary tumors or metastases who have completed brain therapy (such as radiotherapy, stereotactic radiosurgery, or surgical resection) and have remained clinically stable, asymptomatic, and off of steroids for 2 weeks prior to Cycle 1 Day 1 will be eligible.
Male or female participants age 2 years to less than18 years and less than or equal to 25 years for osteosarcoma subjects at the time of informed consent.
Lansky play score greater than or equal to 50% or Karnofsky Performance Status score greater than or equal to 50%. Use Karnofsky for participants greater than or equal to 16 years of age and Lansky for participants less than 16 years of age.
Life expectancy greater than or equal to 3 months.
Adequate bone marrow function as evidenced by:
1. absolute neutrophil count (ANC) greater than or equal to 1.0 x 10^9/L (for Cohorts 3A and 3B leucocyte count greater than or equal to 2 x 10^9/L; participants with bone marrow involvement should have ANC greater than or equal to 0.8 x 10^9/L and leucocyte count greater than or equal to 1 x 10^9/L).
2. hemoglobin greater than or equal to 8.0 grams/deciliter (g/dL) (a hemoglobin less than 8.0 g/dL is acceptable if it is corrected by growth factor or transfusion before starting lenvatinib).
3. platelet count greater than or equal to 75 x 10^9/L.
Adequate liver function as evidenced by:
1. bilirubin less than or equal 1.5 times the upper limit of normal (ULN).
2. alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 times ULN.
Adequate renal function as evidenced by:

a) Serum creatinine based on age/gender as below. If serum creatinine is greater than maximum serum creatinine for age/gender as shown in the table below, then creatinine clearance (or radioisotope glomerular filtration rate [GFR]) must be greater than 70 milliliter/minute/1.73 square meter (mL/min/1.73 m2).

Maximum Serum Creatinine in milligrams/deciliter (mg/dL) for male:

i. Age 2 to less than 6 years = 0.8

ii. Age 6 to less than 10 years = 1.0

iii. Age 10 to less than 13 years = 1.2

iv. Age 13 to less than 16 years = 1.5

v. Age greater than or equal to 16 years = 1.7

Maximum Serum Creatinine (mg/dL) for Female:

vi. Age 2 to less than 6 years = 0.8

vii. Age 6 to less than 10 years = 1.0

viii. Age 10 to less than 13 years = 1.2

ix. Age 13 to less than 16 years = 1.4

x. Age greater than or equal to 16 years = 1.4

The threshold creatinine values in this Table were derived from the Schwartz formula for estimating glomerular filtration rate using child length and stature data published by the CDC.

b) Urine dipstick less than 2+ for proteinuria. Participants who have greater than or equal to 2+ proteinuria on dipstick urinalysis should undergo a spot protein-creatinine (P/C) ratio that should be Grade less than 2.

c) No clinical evidence of nephrotic syndrome.
Adequate cardiac function as evidenced by left ventricular ejection fraction (LVEF) greater than or equal to 50%) at baseline as determined by echocardiography.
Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as:

BP less than 95th percentile for sex, age, and height/length at screening (as per National Heart Lung and Blood Institute guidelines) and no change in antihypertensive medications within 1-week prior to Cycle 1/Day 1. Osteosarcoma subjects 18 to 25 years should have BP ≤150/90 mm Hg at screening and no change in antihypertensive therapy within 1 week prior to Cycle 1/Day 1.
Washout of 3 weeks in case of prior chemotherapy, 6 weeks if treatment included nitrosoureas; 4 weeks for definitive radiotherapy, and 2 weeks for palliative radiotherapy; 3 months from high-dose chemotherapy and stem cell rescue; 3 weeks from major surgery. Participants must have recovered from the acute toxic effects of all prior anticancer therapy before enrollment into the study.
Written and signed informed consent from the parent(s) or legal representative (guardian) and assent from the minor participant. Written informed consent from subjects ≥18 years.
Willing and able to comply with the protocol, scheduled follow-up, and management of toxicity as judged by the Investigator.

Cohort 3B (Combination Expansion): Osteosarcoma subjects who progressed in Cohorts 1 or 2B and opt to receive combination therapy.
Osteosarcoma participants receiving combination therapy of lenvatinib with ifosfamide and etoposide should meet only Inclusion Criteria Numbers 6 through 17 (after progression in Cohort 2B).

Exclusion criteria:

Any active infection or infectious illness unless fully recovered prior to dosing.
Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study.
Other organ toxicity due to prior anticancer therapy (investigational agent, chemotherapy, or radiation therapy) except alopecia, and ototoxicity due to cisplatin not already covered in the inclusion/exclusion criteria, which has not recovered to Grade less than 2 per Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Known hypersensitivity to any component of the product (lenvatinib or ingredients).
Concurrent administration of any other antitumor therapy.
Previous treatment with lenvatinib (except for participants previously enrolled into Cohorts 1 or 2B of this study).
Two or more prior vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) targeted therapies.
Currently receiving any investigational drug or device in another clinical trial or within 30 days preceding informed consent.
A clinically significant ECG abnormality, including a marked baseline prolonged QT or QTc interval (eg, a repeated demonstration of a QTc interval greater than 480 msec).
Gastrointestinal malabsorption or any other condition that in the opinion of the investigator might affect the absorption of lenvatinib.
Gastrointestinal bleeding or active hemoptysis (bright red blood of at least half teaspoon) within 3 weeks prior to the first dose of study drug.
Active second malignancy within 2 years prior to enrollment ([in addition to the primary tumor types specified by cohort in Inclusion Criterion Number 1], but not including definitively treated superficial melanoma, in-situ, basal or squamous cell carcinoma of the skin).
Previous treatment with ifosfamide and Grade greater than or equal to 3 nephrotoxicity or encephalopathy (Cohorts 3A and 3B).
Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.

Cohort 3B (Combination Expansion): Osteosarcoma participants who progressed in Cohorts 1 or 2B and opt to receive combination therapy.
Osteosarcoma participants receiving combination therapy of lenvatinib with ifosfamide and etoposide should meet all the exclusion criteria, with the exception of Criterion Number 6.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Texas Children's Hospital		Houston	Texas	77030	United States
CHU Strasbourg - Hopital Hautepierre

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
34562750	Derived	Gaspar N, Campbell-Hewson Q, Gallego Melcon S, Locatelli F, Venkatramani R, Hecker-Nolting S, Gambart M, Bautista F, Thebaud E, Aerts I, Morland B, Rossig C, Canete Nieto A, Longhi A, Lervat C, Entz-Werle N, Strauss SJ, Marec-Berard P, Okpara CE, He C, Dutta L, Casanova M. Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)☆. ESMO Open. 2021 Oct;6(5):100250. doi: 10.1016/j.esmoop.2021.100250. Epub 2021 Sep 22.
34416160

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants(age group 2 to<6 years and 6 to<18 years)with relapsed or refractory solid malignant tumors received lenvatinib 11mg/m^2(per BSA, daily dose capped at 24 milligram per day[mg/day])as capsules or suspension(lenvatinib capsules dissolved in water/apple juice for participants who were unable to swallow capsules and given as suspension),orally,once daily on Days 1 to 28 of each treatment cycle until progressive disease(PD),intolerable toxicity,participant noncompliance with safety/efficacy assessments,initiation of another anticancer therapy,voluntary discontinuation by participant at any time,or study termination by sponsor,whichever occurred first. Eligible participants of age group 2 to<6 years first underwent 21days run-in period with lenvatinib 5mg/m^2,once daily before receiving lenvatinib11 mg/m^2 in Cycle1 in Cohort1. Duration of each treatment cycle in Cohort1=28 days.After determining recommended dose(RD)in Cohort1,participants were enrolled in Cohorts 2A,2B and 3A.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED	The Participants Flow module (including deaths in reasons for not completed) presentation is based on full analysis set. (Full analysis set included all enrolled participants who did not fail study screening).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 22, 2019	Jun 26, 2023

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Cohort 1: Single-Agent Dose-Finding

Full analysis set included all enrolled participants who did not fail study screening.

Arm/Group Information

ID	Title	Description
BG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Eligible participants of age group 2 to <6 years first underwent 21-days run-in period with lenvatinib 5 mg/m^2, once daily before receiving lenvatinib 11 mg/m^2 in Cycle 1 in Cohort 1. Duration of each treatment cycle in Cohort 1=28 days. After determining RD in Cohort 1, participants were enrolled in Cohorts 2A, 2B and 3A.
BG001	Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2	Participants (age group 2 to <6 years and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 14 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Eligible participants of age group 2 to <6 years first underwent 21-days run-in period with lenvatinib 5 mg/m^2, once daily before receiving lenvatinib 14 mg/m^2 in Cycle 1 in Cohort 1. Duration of each treatment cycle in Cohort 1=28 days. After determining RD in Cohort 1, participants were enrolled in Cohorts 2A, 2B and 3A.
BG002	Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2	Participants (of age group 6 to <18 years) with relapsed or refractory solid malignant tumors received dose of lenvatinib 17 mg/m^2 (administered per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days. After determining the RD in Cohort 1, participants were enrolled in Cohorts 2A, 2B and 3A.
BG003	Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2	Participants with 131 iodine-refractory DTC received lenvatinib 14 mg/m^2 (administered per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 2A=28 days.
BG004	Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2	Participants with relapsed or refractory osteosarcoma received lenvatinib 14 mg/m^2 (administered per BSA with daily dose capped at 24 mg/day) as capsule or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 2B=28 days.
BG005	Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2	Participants with relapsed or refractory osteosarcoma received lenvatinib 11 mg/m^2 (20% lower than the RD from Cohort 1; administered per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 21 of each treatment cycle in combination with ifosfamide 3000 mg/m^2/day intravenously and etoposide 100 mg/m^2/day intravenously on Days 1 to 3 of each treatment cycle for up to a total of 5 cycles as a combination therapy. Duration of each treatment cycle in Cohort 3A=21 days. After determining the RD in Cohort 3A, participants were enrolled in Cohort 3B.
BG006	Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2	Participants with relapsed or refractory osteosarcoma received lenvatinib 14 mg/m^2 (administrated per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 21 of each treatment cycle in combination with ifosfamide 3000 mg/m^2/day intravenously and etoposide 100 mg/m^2/day intravenously on Days 1 to 3 of each treatment cycle for up to a total of 5 cycles as a combination therapy. Duration of each treatment cycle in Cohort 3A=21 days. After determining the RD in Cohort 3A, participants were enrolled in Cohort 3B.
BG007	Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2	Participants with relapsed or refractory osteosarcoma received lenvatinib 14 mg/m^2 (administrated per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 21 of each treatment cycle in combination with ifosfamide 3000 mg/m^2/day intravenously and etoposide 100 mg/m^2/day intravenously on Days 1 to 3 of each treatment cycle for up to a total of 5 cycles as a combination therapy. Duration of each treatment cycle in Cohort 3B=21 days.
BG008	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

2 to <6 years

Title	Measurements
	BG0001 BG0011 BG0020 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0001 BG0015 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0001 BG0011 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Cohort 1: Recommended Dose (RD) of Lenvatinib

RD was defined as the dose that had a dose limiting toxicity (DLT) rate closest to the targeted 20% rate. DLT was an adverse drug reaction and was assessed according to common terminology criteria for adverse events (CTCAE) version (v) 4.03 defined as 1) Grade 4 neutropenia for greater than or equal to (>=) 7 days, 2) Grade >=3 thrombocytopenia with bleeding, or lasting greater than (>) 7 days, 3) Grade >=3 febrile neutropenia, 4) Next course of chemotherapy delayed for >=7 days, 5) Grade >=3 non-hematologic toxicity persisting >7 days optimal supportive care, 6) Grade 4 hypertension, confirmed systolic or diastolic blood pressure >25 millimeters of mercury (mmHg) above the 95th percentile for age, or an elevated diastolic blood pressure (that is, >95th percentile for age) not controlled by a single antihypertensive medication within 14 days of use, 7) Grade 3 proteinuria, 8) Any recurrent Grade 2 non-hematological toxicity requiring >=2 interruption and dose reductions.

Safety analysis set included all participants who received any study drug and had at least one post-baseline safety evaluation.

Posted

Number

milligram per square meter (mg/m^2)

Cycle 1 (28 days)

ID	Title	Description
OG000	Cohort 1: All Participants	Participants (of age group 2 to <6 years [following the completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received dose of lenvatinib 11 mg/m^2, 14 mg/m^2 or 17 mg/m^2 (administered per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.

Units	Counts
Participants	OG00023

Title

Denominators

Categories

Title	Measurements
	OG00014

Primary

Cohort 2A: Number of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR)

OR was defined as participants with best overall response (BOR) of CR or PR as assessed by investigator based on response evaluation criteria in solid tumors (RECIST) version (v) 1.1. For OR, the BOR was defined as the best response (CR or PR for >4 weeks) recorded from the start of the treatment until PD or death whichever occurred first. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

Full analysis set included all enrolled participants who did not fail study screening.

Posted

Count of Participants

Participants

From date of first dose of study drug until first documentation of PD or death, whichever occurred first (until the data cut-off date, 31 May 2019)

ID	Title	Description
OG000	Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2	Participants with 131 iodine-refractory DTC received lenvatinib 14 mg/m^2 (administered per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 2A=28 days.

Primary

Cohort 2A: Number of Participants With Best Overall Response (BOR)

BOR was defined as the best response of CR or PR for >4 weeks or SD for >=7 weeks recorded from the start of the treatment until PD or death, whichever occurred first based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

Full analysis set included all enrolled participants who did not fail study screening.

Posted

Count of Participants

Participants

From first dose of study drug until PD or death, whichever occurred first (until the data cut-off date, 31 May 2019)

ID	Title	Description
OG000	Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2	Participants with 131 iodine-refractory DTC received lenvatinib 14 mg/m^2 (administered per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 2A=28 days.

Primary

Cohorts 2B and 3B: Progression-free Survival (PFS) Rate at Month 4

Progression free survival at Month 4 (PFS-4) rate was defined as the percentage of participants who were alive and without PD at Month 4 after the first dose of study drug, based on RECIST v1.1, using a binomial proportion with corresponding 95% confidence interval (CI). PD: >= 20% increase in sum of diameters of target lesions, reference-smallest sum recorded in study (sum at baseline if that was smallest). Sum of diameters must have absolute increase of >=5 mm. Appearance of >=1 new lesions also considered PD.

PFS-4 evaluable set included all participants treated with study drug for at least 4 months or those who died or radiologically progressed within 4 months after first dose, or received anticancer treatment within 4 months after first dose.

Posted

Number

95% Confidence Interval

percentage of participants

At Month 4

ID	Title	Description
OG000	Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2	Participants with relapsed or refractory osteosarcoma received lenvatinib 14 mg/m^2 (administered per BSA with daily dose capped at 24 mg/day) as capsule or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 2B=28 days.

Primary

Cohort 3A: Recommended Dose (RD) of Lenvatinib When Given in Combination With Etoposide and Ifosfamide

RD of lenvatinib when given in combination with ifosfamide and etoposide was defined as dose that resulted in no more than 1 DLT per 6 participants,or hematologic DLT in 1 participant and nonhematologic DLT in another participant per 6 participants,upon repeating same dose level.DLT was adverse drug reaction and assessed per CTCAE v4.03 defined as 1)Grade 4 neutropenia for >=10 days,2)Grade >=3 thrombocytopenia with bleeding,or lasting >=10 days,3)Grade >=3 febrile neutropenia lasting >=7 days,4)Next course of chemotherapy delayed for >=7 days,5)Grade >=3 nonhematologic toxicity persisting >7 days despite optimal supportive care,6)Grade 4 hypertension,confirmed systolic or diastolic blood pressure >25 mmHg above 95th percentile for age,or elevated diastolic blood pressure(>95th percentile for age)not controlled by single antihypertensive medication within 14 days use,7)Grade 3 proteinuria,8)Any recurrent Grade 2 nonhematological toxicity requiring >=2 interruption and dose reductions.

Safety analysis set included all participants who received any study drug and had at least one post-baseline safety evaluation.

Posted

Number

milligram per square meter (mg/m^2)

Cycle 1 (21 days)

ID	Title	Description
OG000	Cohort 3A: All Participants	Participants with relapsed or refractory osteosarcoma received lenvatinib 11 mg/m^2 (20% lower than the RD from Cohort 1) or 14 mg/m^2, administered per BSA with daily dose capped at 24 mg/day as capsule or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 21 of each treatment cycle, in combination with ifosfamide 3000 mg/m^2/day intravenously and etoposide 100 mg/m^2/day intravenously on Days 1 to 3 of each treatment cycle for up to a total of 5 cycles as combination therapy. Duration of each treatment cycle in Cohort 3A=21 days.

Secondary

Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR)

BOR: best response of CR or PR for >4 weeks or SD for >=7 weeks from first dose, recorded from start of treatment until PD or death, whichever occurred first based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have reduction in their short axis <10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Not evaluable (NE) means BOR of NE or SD of <7 weeks duration. Unknown means no data were available on the case report form.

Full analysis set included all enrolled participants who did not fail study screening. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Posted

Count of Participants

Participants

From date of first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.

Secondary

Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR)

ORR was defined as the percentage of participants with a BOR of CR or PR for >4 weeks or SD for >=7 weeks as assessed by investigator based on RECIST v1.1, recorded from start of study treatment until PD or death whichever occurred first. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. 95% CI of the ORR were calculated according to Clopper and Pearson method.

Posted

Number

95% Confidence Interval

percentage of participants

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.

Secondary

Cohorts 1, 2A, 2B, 3A and 3B: Duration of Response (DOR)

DOR was defined as time in months from the first documentation confirmed CR or PR until the first documentation of confirmed PD as assessed by investigator based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. 95% CI for the median were calculated according to Brookmeyer and Crowley method.

Full analysis set included all enrolled participants who did not fail study screening. Here "overall number of participants analyzed, N" signifies participants who were evaluable for this measure. Here, "N" for Cohort 1 (Lenvatinib 11, 14, 17 mg/m^2) and Cohort 3A (Lenvatinib 14 mg/m^2) is zero as there were no events of CR or PR in these arms.

Posted

Median

95% Confidence Interval

months

First documentation of CR/PR until first documentation of PD (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.

Secondary

Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control

Participants were defined as having disease control if they had a BOR of CR or PR for >4 weeks, or SD (minimum duration from first dose to SD >=7 weeks) or if participants had a BOR of CR or Non-CR/Non-PD (minimum duration from first dose to Non-CR/Non-PD >=7 weeks) per RECIST v1.1, recorded from first dose until PD or death whichever occurred first. CR: disappearance of all target/non-target lesions (non-lymph nodes). All pathological lymph nodes (target/non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest SOD. Non-CR/Non-PD: persistence of 1 or more non-target lesions, maintenance of tumor marker level above the normal limits.

Full analysis set included all enrolled participants who did not fail study screening.

Posted

Count of Participants

Participants

From first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.

Secondary

Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit

Participants were defined as having clinical benefit if they had a BOR of CR or PR for >4 weeks or durable SD (lasting >=23 weeks) or if participants had a BOR of CR or durable Non-CR/Non-PD (lasting >=23 weeks) as per RECIST v1.1, recorded from first dose until PD or death whichever occurred first. CR: disappearance of all target/non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target/non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. Non-CR/Non-PD:persistence of 1 or more non-target lesions and maintenance of tumor marker level above the normal limits.

Full analysis set included all enrolled participants who did not fail study screening.

Posted

Count of Participants

Participants

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.

Secondary

Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS)

PFS was defined as the time (in months) from the date of first dose of study drug to the date of first documentation of PD or date of death, whichever occurred first, based on RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the baseline SOD of target lesions. 95% CI of median were calculated according to Brookmeyer and Crowley method.

Full analysis set included all enrolled participants who did not fail study screening.

Posted

Median

95% Confidence Interval

months

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.

Secondary

Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP)

TTP was defined as the time from the date of first dose of study drug to the date of first documentation of PD based on RECIST 1.1. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the baseline SOD of target lesions. 95% CI of median were calculated according to Brookmeyer and Crowley method.

Full analysis set included all enrolled participants who did not fail study screening.

Posted

Median

95% Confidence Interval

months

From first dose of study drug until PD (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.

Secondary

Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS)

OS was defined as the time from the date of the first dose of study drug until the date of death from any cause. Participants who are lost to follow-up and those who are alive at the date of data cutoff were censored at the date the participant was last known to be alive (or the data cutoff date). 95% CI of median were calculated according to Brookmeyer and Crowley method.

Full analysis set included all enrolled participants who did not fail study screening.

Posted

Median

95% Confidence Interval

months

From first dose of study drug until death (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.
OG001

Secondary

Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Number of participants with TEAEs (serious and non-serious adverse events) and SAEs were reported based on their safety assessments of hematology, clinical chemistry, proximal tibial growth, fecal occult blood, physical examinations, regular measurement of vital signs and electrocardiogram parameter values.

Safety analysis set included all participants who received any study drug and had at least one post-baseline safety evaluation.

Posted

Count of Participants

Participants

From the date of first dose of study drug up to 30 days after the last dose (up to approximately 7 years)

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.
OG001

Secondary

Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria

An aliquot of the urine samples were collected to analyze protein by dipstick method, microscopic examination (if protein was abnormal). The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters of urine protein can be read as "negative, Trace, plus (+) 1, +2, +3 and +4" indicating proportional concentrations in the urine sample. The plus sign increases with a higher level of proteins in the urine.

Safety analysis set included all participants who received any study drug and had at least one post-baseline safety evaluation. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Posted

Count of Participants

Participants

Baseline up to approximately 4 years 7 months

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.

Secondary

Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score

Lansky Performance Play Scale rates a child's activity level for <16 years of age. Scores on scale range from 0 (unresponsive) to 100 ( fully active, normal), where 100=fully active, normal; 90=minor restrictions in physically strenuous activity; 80=active, but tires more quickly; 70=both greater restriction of and less time spent in play activity; 60=up and around, but minimal active play, keeps busy with quieter activities; 50=gets dressed, but lies around much of day, no active play, able to participant in quiet play and activities; 40=mostly in bed, participates in quiet activities; 30=in bed, needs assistance even for quiet play; 20=often sleeping, play entirely limited to very passive activities; 10=no play, does not get out of bed; 0=unresponsive. Higher score indicates more activity and lower indicates less or no activity.

Posted

Count of Participants

Participants

Baseline up to approximately 4 years 7 months

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.

Secondary

Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores

KPS: compare effectiveness of medicine for disease and assess outcomes in participants. KPS Scores: recorded on 11 point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100%), where 0=Dead; 10=moribund, fatal processes progressing rapidly; 20=very sick, hospital admission necessary, active supportive treatment necessary; 30=severely disabled, hospital admission is indicated although death not imminent; 40=disabled, requires special care/assistance; 50=requires considerable assistance/frequent medical care; 60=requires occasional assistance, but is able to care for personal needs; 70=cares for self, unable to carry normal activity or active work; 80=normal activity with effort, some signs of disease; 90=able to carry on normal activity, minor signs of disease; 100=normal no complaints, no evidence of disease. Lower score, worse survival for most serious illnesses.

Posted

Count of Participants

Participants

Baseline up to approximately 4 years 7 months

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.

Secondary

Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib

Duration of each cycle for Cohorts 1, 2A, 2B is 28 days. Duration of each cycle for Cohorts 3A, 3B is 21 days.

Pharmacokinetic (PK) Analysis Set included all participants who had received any study drug and had evaluable PK data. Here "number analyzed, n" signifies participants who were evaluable for this outcome measure at given time points.

Posted

Mean

Standard Deviation

nanogram per milliliter (ng/mL)

Cohorts 1, 2A, 2B: Cycle(C)1 Day(D)1: 0.5-4 hours (h), 6-10 h post-dose, C1D15: pre-dose, 0.5-4 h, 6-10 h post-dose, C2D1: pre-dose, 2-12 h post-dose; Cohorts 3A, 3B: C1D1: 0.5-4 h, 6-10 h post-dose, C2D1: pre-dose, 2-12 h post-dose

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.
OG001

Secondary

Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level

Serum biomarkers included Fibroblast Growth Factor (FGF) 19, FGF 21, Vascular Endothelial Growth Factor (VEGF). In this outcome measure, percent change from baseline in serum biomarkers level per "PFS-4, Yes" and "PFS-4, No" have been reported. As per assessment of investigator based on RECIST v1.1, "PFS-4, Yes"= participants evaluable for PFS-4 month and alive and without PD at 4 months from the first dose, "PFS-4, No"=participants evaluable for PFS-4 month and not alive or with PD at 4 months from the first dose.

PFS-4 evaluable set: all participants treated with study drug for at least 4 months or those who died or radiologically progressed within 4 months after first dose or received anticancer treatment within 4 months after first dose. "N": participants evaluable for this measure. "n": participants who were evaluable for this measure for specific rows.

Posted

Mean

Standard Deviation

percent change

Cohort 2B: Baseline, Cycle 2-3 Day 1 (Duration of each cycle=28 days); Cohort 3B: Baseline, Cycle 2 Day 1, Cycle 4 Day 1 (Duration of each cycle=21 days)

ID	Title	Description
OG000	Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2	Participants with relapsed or refractory osteosarcoma received lenvatinib 14 mg/m^2 (administered per BSA with daily dose capped at 24 mg/day) as capsule or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle=28 days.

Secondary

Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure

TEAEs (serious and non-serious), those occurred most frequently have been reported in this outcome measure. "Palmar-plantar E syndrome" refers to Palmar-plantar erythrodysaesthesia syndrome.

Safety analysis set included all participants who received any study drug and had at least one post-baseline safety evaluation.

Posted

Count of Participants

Participants

First dose of study drug until 30 days after last dose of study drug (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.
OG001

Secondary

Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib

In acceptability questionnaire, participants were asked to answer the overall acceptability of lenvatinib suspension considering the following elements: taste, appearance, smell and how does it feel in the mouth. Overall acceptability was answered in terms of 7 responses: Super good, really good, good, may be good or may be bad, bad, really bad, super bad. Overall acceptability was the overall acceptance for taste, appearance, smell, and the feeling in mouth. In this measure, number of participants have been reported per their overall acceptability responses.

Palatability analysis set included all participants who received oral suspension of lenvatinib and answered at least 1 question in the palatability questionnaire case report form.

Posted

Count of Participants

Participants

Cycle 1 Day 1 (Cycle length=28 days for Cohorts 1, 2A, 2B; Cycle length=21 days for Cohorts 3A, 3B)

ID	Title	Description
OG000	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Lenvatinib 5 mg/m^2	Eligible participants of age group 2 to <6 years first underwent a 21-day run-in period with lenvatinib 5 mg/m^2, once daily as capsule or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension) before receiving lenvatinib 11 mg/m^2 or 14 mg/m^2 in Cycle 1 of Cohort 1 (Single-agent Dose-finding).	0	2	0	2	2	2
EG001	Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.	2	5	3	5	5	5
EG002	Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2	Participants (age group 2 to <6 years [following completion of run-in period] and 6 to <18 years) with relapsed or refractory solid malignant tumors received lenvatinib 14 mg/m^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.	7	11	7	11	11	11
EG003	Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2	Participants (of age group 6 to <18 years) with relapsed or refractory solid malignant tumors received dose of lenvatinib 17 mg/m^2 (administered per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days.	6	7	5	7	7	7
EG004	Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2	Participants with 131 iodine-refractory DTC received lenvatinib 14 mg/m^2 (administered per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 2A=28 days.	0	1	1	1	1	1
EG005	Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2	Participants with relapsed or refractory osteosarcoma received lenvatinib 14 mg/m^2 (administered per BSA with daily dose capped at 24 mg/day) as capsule or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 2B=28 days.	27	31	21	31	29	31
EG006	Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2	Participants with relapsed or refractory osteosarcoma received lenvatinib 11 mg/m^2 (20% lower than the RD from Cohort 1; administered per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 21 of each treatment cycle in combination with ifosfamide 3000 mg/m^2/day intravenously and etoposide 100 mg/m^2/day intravenously on Days 1 to 3 of each treatment cycle for up to a total of 5 cycles as a combination therapy. Duration of each treatment cycle in Cohort 3A=21 days.	10	11	7	11	11	11
EG007	Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2	Participants with relapsed or refractory osteosarcoma received lenvatinib 14 mg/m^2 (administrated per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 21 of each treatment cycle in combination with ifosfamide 3000 mg/m^2/day intravenously and etoposide 100 mg/m^2/day intravenously on Days 1 to 3 of each treatment cycle for up to a total of 5 cycles as a combination therapy. Duration of each treatment cycle in Cohort 3A=21 days.	6	11	9	11	11	11
EG008	Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2	Participants with relapsed or refractory osteosarcoma received lenvatinib 14 mg/m^2 (administrated per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 21 of each treatment cycle in combination with ifosfamide 3000 mg/m^2/day intravenously and etoposide 100 mg/m^2/day intravenously on Days 1 to 3 of each treatment cycle for up to a total of 5 cycles as a combination therapy. Duration of each treatment cycle in Cohort 3B=21 days.	14	20	16	20	20	20

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Disseminated intravascular coagulation	Blood and lymphatic system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG0031 events1 affected7 at risk EG004
Neutropenia	Blood and lymphatic system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Cardio-respiratory arrest	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Enterocolitis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Gait disturbance	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
General physical health deterioration	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pain	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0022 events1 affected11 at risk EG003
Pneumonia	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0021 events1 affected11 at risk EG003
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Amylase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Blood pressure increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Ejection fraction decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Lipase increased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Platelet count decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Weight decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0022 events1 affected11 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0023 events3 affected11 at risk EG003
Depressed level of consciousness	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Spinal cord compression	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0024 events1 affected11 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypertension	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0022 events2 affected11 at risk EG003
Sinus bradycardia	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Diarrhoea	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Gingival bleeding	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Facial pain	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Influenza like illness	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pyrexia	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Dehydration	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Intervertebral disc compression	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pathological fracture	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Headache	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Ischaemic stroke	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Renal pain	Renal and urinary disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0015 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Arterial thrombosis	Vascular disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Lymphoedema	Vascular disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Leukopenia	Blood and lymphatic system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Gastritis	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Stomatitis	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Cholecystitis	Hepatobiliary disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Bacteraemia	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Clostridium difficile infection	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Influenza	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Urinary tract infection	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0015 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Wound infection bacterial	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Accidental overdose	Injury, poisoning and procedural complications	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Brain injury	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Toxic encephalopathy	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Anaemia	Blood and lymphatic system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Bradycardia	Cardiac disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Cardiac failure	Cardiac disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Anal inflammation	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pancreatitis	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Vulvitis	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Allergic transfusion reaction	Injury, poisoning and procedural complications	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Transfusion related complication	Injury, poisoning and procedural complications	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Neutrophil count decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
White blood cell count decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Renal failure	Renal and urinary disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Urinary retention	Renal and urinary disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypotension	Vascular disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Venoocclusive disease	Vascular disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Vascular pseudoaneurysm	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Dysmetria	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Thrombosis	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected5 at risk EG0022 events2 affected11 at risk EG0031 events1 affected7 at risk EG0040 events0 affected1 at risk EG0057 events5 affected31 at risk EG00643 events9 affected11 at risk EG00729 events7 affected11 at risk EG00877 events15 affected20 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Polycythaemia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0021 events1 affected11 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0015 events3 affected5 at risk EG00210 events6 affected11 at risk EG003
Eye ulcer	Eye disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Papilloedema	Eye disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0013 events2 affected5 at risk EG0029 events7 affected11 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Anal haemorrhage	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Anal incontinence	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Anal pruritus	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Aphthous ulcer	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0022 events2 affected11 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0015 events4 affected5 at risk EG0029 events5 affected11 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0021 events1 affected11 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0018 events3 affected5 at risk EG0024 events2 affected11 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Oral dysaesthesia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected5 at risk EG0026 events1 affected11 at risk EG003
Perianal erythema	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Proctalgia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0019 events1 affected5 at risk EG00220 events7 affected11 at risk EG003
Asthenia	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0014 events2 affected5 at risk EG0021 events1 affected11 at risk EG003
Catheter site pain	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Fatigue	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0014 events2 affected5 at risk EG0024 events3 affected11 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0016 events2 affected5 at risk EG0020 events0 affected11 at risk EG003
Oedema peripheral	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pain	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0025 events1 affected11 at risk EG003
Pyrexia	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0018 events2 affected5 at risk EG0029 events4 affected11 at risk EG003
Hepatocellular injury	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Bronchitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Ear infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Gastroenteritis	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Influenza	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Localised infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Rhinitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected2 at risk EG0012 events1 affected5 at risk EG0023 events2 affected11 at risk EG003
Sinusitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Staphylococcal sepsis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected5 at risk EG0021 events1 affected11 at risk EG003
Viral infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Vulvovaginal candidiasis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0021 events1 affected11 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0026 events4 affected11 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0023 events3 affected11 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0022 events2 affected11 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Blood creatinine increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Blood urea increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
C-reactive protein increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0023 events3 affected11 at risk EG003
Ejection fraction decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Lipase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Neutrophil count increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Platelet count decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Red blood cell sedimentation rate increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Weight decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG00113 events3 affected5 at risk EG0026 events3 affected11 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG00114 events4 affected5 at risk EG0029 events5 affected11 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0024 events2 affected11 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0022 events2 affected11 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected5 at risk EG0028 events4 affected11 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0022 events1 affected11 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0021 events1 affected11 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG00112 events2 affected5 at risk EG0022 events2 affected11 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0014 events2 affected5 at risk EG00210 events4 affected11 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected5 at risk EG0022 events1 affected11 at risk EG003
Pericardial effusion malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Cranial nerve paralysis	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Dizziness	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Dysaesthesia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected5 at risk EG0029 events6 affected11 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Lethargy	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Monoparesis	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Muscle contractions involuntary	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Phantom pain	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Pyramidal tract syndrome	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Sciatica	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected5 at risk EG0021 events1 affected11 at risk EG003
Depressed mood	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected5 at risk EG0020 events0 affected11 at risk EG003
Depression	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Sleep disorder	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Bladder pain	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0021 events1 affected11 at risk EG003
Cystitis noninfective	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0022 events2 affected11 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0023 events3 affected11 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG00216 events3 affected11 at risk EG003
Menstruation irregular	Reproductive system and breast disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0022 events1 affected11 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0013 events2 affected5 at risk EG0023 events3 affected11 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0013 events2 affected5 at risk EG0020 events0 affected11 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0013 events2 affected5 at risk EG0023 events3 affected11 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0016 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0021 events1 affected11 at risk EG003
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0021 events1 affected11 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0011 events1 affected5 at risk EG0021 events1 affected11 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0011 events1 affected5 at risk EG0021 events1 affected11 at risk EG003
Hair colour changes	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0021 events1 affected11 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0014 events2 affected5 at risk EG0022 events2 affected11 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0024 events2 affected11 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0021 events1 affected11 at risk EG003
Spider naevus	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Flushing	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypertension	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected5 at risk EG0023 events3 affected11 at risk EG003
Hypotension	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Thyroglobulin increased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Insomnia	Psychiatric disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Acne	Skin and subcutaneous tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Left ventricular dysfunction	Cardiac disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Anal fissure	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Eructation	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Toothache	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Nasopharyngitis	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Pharyngitis	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Blood thyroid stimulating hormone increased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Electrocardiogram QT prolonged	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Neuralgia	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Somnolence	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Leukopenia	Blood and lymphatic system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Sinus bradycardia	Cardiac disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Tachycardia	Cardiac disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Tinnitus	Ear and labyrinth disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hyperthyroidism	Endocrine disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Diplopia	Eye disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Dry eye	Eye disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Eye pain	Eye disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Eyelid oedema	Eye disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Ocular hyperaemia	Eye disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Photophobia	Eye disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Vision blurred	Eye disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Anal fistula	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Anal inflammation	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Anal skin tags	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Diarrhoea haemorrhagic	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Gastritis	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Glossitis	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Haematochezia	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Haemorrhoids	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypoaesthesia oral	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Oesophageal obstruction	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Oral discomfort	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Oral pain	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Proctitis	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Catheter site bruise	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Catheter site dermatitis	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Catheter site swelling	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Chills	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Device related thrombosis	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Face oedema	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Influenza like illness	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Infusion site irritation	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Localised oedema	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Malaise	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Swelling	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Clostridium difficile infection	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Cystitis	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Device related infection	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Eye infection bacterial	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Gingivitis	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Oral herpes	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Osteomyelitis	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Paronychia	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pseudomonas infection	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Rash pustular	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Staphylococcal infection	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Vascular device infection	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Allergic transfusion reaction	Injury, poisoning and procedural complications	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Fall	Injury, poisoning and procedural complications	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Limb injury	Injury, poisoning and procedural complications	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Wound	Injury, poisoning and procedural complications	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Wound complication	Injury, poisoning and procedural complications	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Wound dehiscence	Injury, poisoning and procedural complications	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Blood calcium decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Blood magnesium decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Blood phosphorus increased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Blood potassium decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Haemoglobin decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Lymphocyte count decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Neutrophil count decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Thyroxine decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Urine output decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
White blood cell count decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Dehydration	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Electrolyte imbalance	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypermagnesaemia	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypoproteinaemia	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Metabolic acidosis	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Vitamin D deficiency	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Coccydynia	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Periostitis	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Amputation stump pain	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Generalised tonic-clonic seizure	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Migraine	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Paraesthesia	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Presyncope	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Sensory disturbance	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Syncope	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Toxic encephalopathy	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Tremor	Nervous system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Agitation	Psychiatric disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Confusional state	Psychiatric disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Irritability	Psychiatric disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Glycosuria	Renal and urinary disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Renal impairment	Renal and urinary disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Renal tubular disorder	Renal and urinary disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Balanoposthitis	Reproductive system and breast disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Vulvovaginal pruritus	Reproductive system and breast disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Dysaesthesia pharynx	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pharyngeal inflammation	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Dermatitis bullous	Skin and subcutaneous tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Scab	Skin and subcutaneous tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Lymphoedema	Vascular disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Acquired antithrombin III deficiency	Blood and lymphatic system disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Bradycardia	Cardiac disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Ventricular dysfunction	Cardiac disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Eye discharge	Eye disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Dry mouth	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Dyschezia	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Haematemesis	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Noninfective gingivitis	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pancreatitis	Gastrointestinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Axillary pain	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Chest pain	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Inflammation	General disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Cellulitis	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Eyelid infection	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Folliculitis	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Gastrointestinal infection	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Oesophageal candidiasis	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pneumonia	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Vaginal infection	Infections and infestations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Amylase increased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Blood phosphorus decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Blood uric acid decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Culture stool positive	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Full blood count decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Lipase decreased	Investigations	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Acidosis	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Cachexia	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Fluid retention	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hyperphosphataemia	Metabolism and nutrition disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Limb mass	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Spinal pain	Musculoskeletal and connective tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Nightmare	Psychiatric disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Leukocyturia	Renal and urinary disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Renal failure	Renal and urinary disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Urine flow decreased	Renal and urinary disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Genital pain	Reproductive system and breast disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Dermatitis allergic	Skin and subcutaneous tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Onychalgia	Skin and subcutaneous tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Rash generalised	Skin and subcutaneous tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Capillary leak syndrome	Vascular disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Haematoma	Vascular disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hot flush	Vascular disorders	21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Bundle branch block right	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Cardiotoxicity	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Anal fissure haemorrhage	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Gastrointestinal pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Paraesthesia oral	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Injection site mass	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Sensation of foreign body	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Anal fungal infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Angular cheilitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Catheter site infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Genital candidiasis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Genital infection fungal	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Tonsillitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Anaemia postoperative	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Post procedural complication	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Vaccination complication	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0015 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Brain natriuretic peptide increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Coronavirus test positive	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Electrocardiogram PR prolongation	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Occult blood positive	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Thyroxine increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Weight increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
White blood cell count increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypochloraemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hyperamylasaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Muscle atrophy	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Muscle rigidity	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Major depression	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Mood altered	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Albuminuria	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Nephropathy toxic	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Amenorrhoea	Reproductive system and breast disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Genital lesion	Reproductive system and breast disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected5 at risk EG0020 events0 affected11 at risk EG003
Perineal pain	Reproductive system and breast disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Premature menopause	Reproductive system and breast disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Itching scar	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Palmar erythema	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Scar pain	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Umbilical discharge	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Purpura	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Cardiac dysfunction	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Systolic dysfunction	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Gingival bleeding	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Abscess limb	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003
Superior vena cava syndrome	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected5 at risk EG0020 events0 affected11 at risk EG003

ID	Term
D009369	Neoplasms
D012516	Osteosarcoma

ID	Term
C531958	lenvatinib
D007069	Ifosfamide
D005047	Etoposide

Ancestor Terms

ID	Term
D003520	Cyclophosphamide
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D010078	Oxazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011034	Podophyllotoxin
D013764	Tetrahydronaphthalenes
D009281	Naphthalenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D011083	Polycyclic Compounds
D005960	Glucosides
D006027	Glycosides
D002241	Carbohydrates

EG0050 events0 affected31 at risk

EG0060 events0 affected11 at risk

EG0070 events0 affected11 at risk

EG0080 events0 affected20 at risk