A Study of Vismodegib in Patients With Relapsed/Refractor... | NCT01880437

ID	Type	Description	Link
2013-001570-14	EudraCT Number

Label	Type	Description	Intervention Names
Vismodegib	Experimental		Drug: cytarabine Drug: vismodegib

Name	Type	Description	Arm Group Labels	Other Names
cytarabine	Drug	Cohort 2: 20 mg sc daily for 10 days starting Day 1, with a possible further cycle of 20 mg sc daily for 5 days starting no earlier than Day 29	Vismodegib

Measure	Description	Time Frame
Percentage of Participants With a Complete Response (CR) or CR With Incomplete Blood Count Recovery (CRi) or Morphologic Leukemia Free State (MLFS) or Partial Response (PR) at Week 8	CR was defined as achieved if the neutrophils count was greater than (>) 1000 cells per microliter (µL), platelets count >100000/µL, bone marrow blasts percentage (%) less than (<) 5, no Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts), no transfusion requirements and no signs of extra medullary disease (EMD). CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils >1000 cells/µL or Not applicable [NA] or platelets count >100000/µL or NA), bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. MLFS (neutrophil and platelet criteria were NA) was defined as bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. PR was defined as neutrophils count >1000 cells/µL, platelets count >100000/µL, and >50% decrease from baseline to a range of 5-25% of bone marrow blasts or blasts <5% with Auer rods.	Week 8

Measure	Description	Time Frame
Percentage of Participants With CR, CRi, MLFS or PR at Anytime During Study Treatment	CR was defined as achieved if the neutrophils count >1000 cells/µL, platelets count >100000/µL, bone marrow blasts <5%, no Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts), no transfusion requirements and no signs of EMD. CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils > 1000 cells/µL or NA or platelets count >100000/µL or NA, bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. MLFS (neutrophil and platelet criteria were NA) was defined as bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. PR was defined as neutrophils count >1000 cells/µL, platelets count >100000/µL, and >50% decrease from baseline to a range of 5-25% of bone marrow blasts or blasts <5% with Auer rods. The 95% confidence intervals (CI) were constructed using Blyth-Still-Cassella method.

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Stanford	California	94305	United States

ID	Title	Description
FG000	Poor Risk Cytogenetics	Participants with relapsed/refractory acute myeloid leukemia (AML) or relapsed/refractory high-risk myelodysplastic syndrome (MDS) falling under 'poor risk cytogenetics' subgroup received oral 150 milligrams (mg) dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.

ID	Title	Description
BG000	Poor Risk Cytogenetics	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
BG001	FLT-3 Mutation Positive	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
BG002	Neither Poor Risk Cytogenetics Nor FLT-3	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00015 BG0014 BG00219 BG00338

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

Percentage of Participants With a Complete Response (CR) or CR With Incomplete Blood Count Recovery (CRi) or Morphologic Leukemia Free State (MLFS) or Partial Response (PR) at Week 8

CR was defined as achieved if the neutrophils count was greater than (>) 1000 cells per microliter (µL), platelets count >100000/µL, bone marrow blasts percentage (%) less than (<) 5, no Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts), no transfusion requirements and no signs of extra medullary disease (EMD). CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils >1000 cells/µL or Not applicable [NA] or platelets count >100000/µL or NA), bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. MLFS (neutrophil and platelet criteria were NA) was defined as bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. PR was defined as neutrophils count >1000 cells/µL, platelets count >100000/µL, and >50% decrease from baseline to a range of 5-25% of bone marrow blasts or blasts <5% with Auer rods.

As the primary efficacy time-point (Week 8) was not reached for all participants due to study termination based on interim data analysis, the analysis of this outcome measure could not be performed, as per planned analysis.

Posted

Week 8

ID	Title	Description
OG000	Poor Risk Cytogenetics	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
OG001	FLT-3 Mutation Positive	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
OG002	Neither Poor Risk Cytogenetics Nor FLT3	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.

Units	Counts
Participants	OG0000 OG0010 OG0020

Secondary

Percentage of Participants With CR, CRi, MLFS or PR at Anytime During Study Treatment

CR was defined as achieved if the neutrophils count >1000 cells/µL, platelets count >100000/µL, bone marrow blasts <5%, no Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts), no transfusion requirements and no signs of EMD. CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils > 1000 cells/µL or NA or platelets count >100000/µL or NA, bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. MLFS (neutrophil and platelet criteria were NA) was defined as bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. PR was defined as neutrophils count >1000 cells/µL, platelets count >100000/µL, and >50% decrease from baseline to a range of 5-25% of bone marrow blasts or blasts <5% with Auer rods. The 95% confidence intervals (CI) were constructed using Blyth-Still-Cassella method.

Efficacy analysis population included all enrolled participants. Here "number of participants analyzed" included participants who were evaluable for tumor response at anytime during the study.

Posted

Number

95% Confidence Interval

percentage of participants

Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)

ID	Title	Description
OG000	Poor Risk Cytogenetics	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.

Secondary

Duration of Overall Response (DOR)

DOR is defined as the time from the first occurrence of a documented overall response to the time of relapse, as determined by the investigator using International Working Group (IWG) criteria (Participants not falling under any of the response criteria [CR or CRi or MLFS or PR] described under outcome measure 1 were considered as non-responders) or death from any cause during the study (defined as death within 30 days after the last dose of study drug).

Efficacy population including participants who were considered as responders.

Posted

Median

95% Confidence Interval

weeks

Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)

ID	Title	Description
OG000	Poor Risk Cytogenetics	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
OG001	FLT-3 Mutation Positive	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.

Secondary

Median Overall Survival (OS) Time

OS was defined as the time from start of study drug to death from any cause. OS was estimated using Kaplan-Meier analysis. Participants alive at the last date known to be alive were censored for the analysis.

Efficacy analysis population.

Posted

Median

95% Confidence Interval

months

Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)

ID	Title	Description
OG000	Poor Risk Cytogenetics	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
OG001	FLT-3 Mutation Positive	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
OG002	Neither Poor Risk Cytogenetics Nor FLT-3	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.

Secondary

Percentage of Participants With an Event of Death During the Study

Efficacy analysis population.

Posted

Number

percentage of participants

Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)

ID	Title	Description
OG000	Poor Risk Cytogenetics	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
OG001	FLT-3 Mutation Positive	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
OG002	Neither Poor Risk Cytogenetics Nor FLT-3	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.

Secondary

Pharmacokinetics (PK): Steady-state Plasma Concentration of Vismodegib

PK data was planned to be reported only if the results of Cohort 2 are available.

As the study was terminated prior to Cohort 2 enrollment, PK analysis could not be performed, as planned.

Posted

Predose on Days 8, 29 and 57

ID	Title	Description
OG000	Poor Risk Cytogenetics	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
OG001	FLT-3 Mutation Positive	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
OG002	Neither Poor Risk Cytogenetics Nor FLT-3	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.

Secondary

Area Under the Concentration-time Curve (AUC) of Cytarabine

PK data was planned to be reported only if the results of Cohort 2 are available.

No participants were enrolled as the study was terminated prior to the initiation of Cohort 2.

Posted

Predose, 0.25, 0.5, 1, 3, 6 hours post-dose on Days 1, 8 and 29

ID	Title	Description
OG000	Planned Cohort 2	Participants in Cohort 2 were planned to receive low-dose subcutaneous injections of cytarabine in combination with continuous daily vismodegib (150 mg orally).

Units	Counts
Participants	OG0000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0011 affected4 at risk EG0024 affected19 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0011 affected4 at risk EG0020 affected19 at risk
Haemoglobinaemia	Blood and lymphatic system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0012 affected4 at risk EG0022 affected19 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0023 affected19 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0010 affected4 at risk EG0023 affected19 at risk
Angina pectoris	Cardiac disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Pericardial effusion	Cardiac disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Sinus tachycardia	Cardiac disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Tachycardia	Cardiac disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Cerumen impaction	Ear and labyrinth disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Hearing impaired	Ear and labyrinth disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Eye haemorrhage	Eye disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Eye pruritus	Eye disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Ocular hyperaemia	Eye disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Scleral discolouration	Eye disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0004 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0022 affected19 at risk
Anal fissure	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Aphthous stomatitis	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Breath odour	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected19 at risk
Cheilitis	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Constipation	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0004 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Dental caries	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0026 affected19 at risk
Dry mouth	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected19 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected19 at risk
Faecal incontinence	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Haematochezia	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0021 affected19 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Melaena	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Nausea	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0004 affected15 at risk EG0010 affected4 at risk EG00210 affected19 at risk
Oesophageal pain	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Oral pain	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Salivary hypersecretion	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Toothache	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Vomiting	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0011 affected4 at risk EG0024 affected19 at risk
Asthenia	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Catheter site pain	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Chest discomfort	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Chest pain	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Chills	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0011 affected4 at risk EG0022 affected19 at risk
Early satiety	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Fatigue	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0012 affected4 at risk EG0025 affected19 at risk
Feeling cold	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Localised oedema	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Malaise	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Mucosal dryness	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Mucosal inflammation	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Multi-organ failure	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Non-cardiac chest pain	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Oedema	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Oedema peripheral	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0004 affected15 at risk EG0010 affected4 at risk EG0024 affected19 at risk
Pain	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0023 affected19 at risk
Peripheral swelling	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Pyrexia	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0003 affected15 at risk EG0013 affected4 at risk EG0025 affected19 at risk
Candida infection	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Catheter site infection	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Cellulitis	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Clostridium difficile infection	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Enterococcal infection	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Erysipelas	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Escherichia bacteraemia	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Herpes simplex	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Influenza	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Liver abscess	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Localised infection	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Mucosal infection	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Oral candidiasis	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Oral fungal infection	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Oral herpes	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Post procedural infection	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Rhinitis	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Staphylococcal infection	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0021 affected19 at risk
Tooth infection	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Allergic transfusion reaction	Injury, poisoning and procedural complications	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Scratch	Injury, poisoning and procedural complications	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected19 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Alanine aminotransferase increased	Investigations	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Blood bilirubin increased	Investigations	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Blood creatinine increased	Investigations	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
C-reactive protein increased	Investigations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Cardiac murmur	Investigations	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Liver function test abnormal	Investigations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Neutrophil count decreased	Investigations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Platelet count decreased	Investigations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Weight decreased	Investigations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (17.1)	Non-systematic Assessment	EG0004 affected15 at risk EG0011 affected4 at risk EG0024 affected19 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (17.1)	Non-systematic Assessment	EG0003 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0011 affected4 at risk EG0021 affected19 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0011 affected4 at risk EG0021 affected19 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0011 affected4 at risk EG0026 affected19 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (17.1)	Non-systematic Assessment	EG0003 affected15 at risk EG0010 affected4 at risk EG0023 affected19 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0011 affected4 at risk EG0022 affected19 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Vitamin B12 deficiency	Metabolism and nutrition disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0011 affected4 at risk EG0021 affected19 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected19 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0003 affected15 at risk EG0011 affected4 at risk EG0025 affected19 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0010 affected4 at risk EG0023 affected19 at risk
Acrochordon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Chloroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Dizziness	Nervous system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0010 affected4 at risk EG0026 affected19 at risk
Dysgeusia	Nervous system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0004 affected15 at risk EG0011 affected4 at risk EG0027 affected19 at risk
Headache	Nervous system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0011 affected4 at risk EG0021 affected19 at risk
Hyperaesthesia	Nervous system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Orthostatic intolerance	Nervous system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Radicular pain	Nervous system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Restless legs syndrome	Nervous system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Sinus headache	Nervous system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Somnolence	Nervous system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Depression	Psychiatric disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Disorientation	Psychiatric disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Insomnia	Psychiatric disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Mental status changes	Psychiatric disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Restlessness	Psychiatric disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Sleep disorder	Psychiatric disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Haematuria	Renal and urinary disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Pollakiuria	Renal and urinary disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Vulval ulceration	Reproductive system and breast disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Vulvovaginal pain	Reproductive system and breast disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0023 affected19 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0003 affected15 at risk EG0010 affected4 at risk EG0023 affected19 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0022 affected19 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0028 affected19 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0003 affected15 at risk EG0011 affected4 at risk EG0021 affected19 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0021 affected19 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0023 affected19 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0011 affected4 at risk EG0022 affected19 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Snoring	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0002 affected15 at risk EG0011 affected4 at risk EG0021 affected19 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0021 affected19 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Petechiae	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0011 affected4 at risk EG0021 affected19 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected19 at risk
Flushing	Vascular disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Haematoma	Vascular disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0023 affected19 at risk
Hypertension	Vascular disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0022 affected19 at risk
Hypotension	Vascular disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0024 affected19 at risk
Subclavian vein thrombosis	Vascular disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk
Vasculitis	Vascular disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected19 at risk

ID	Term
D009190	Myelodysplastic Syndromes
D007951	Leukemia, Myeloid

ID	Term
D001855	Bone Marrow Diseases
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms

ID	Term
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D001087	Arabinonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Poor Risk Cytogenetics	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.	10	15	13	15
EG001	FLT-3 Mutation Positive	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.	3	4	4	4
EG002	Neither Poor Risk Cytogenetics Nor FLT-3	Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.	13	19	19	19