Efficacy and Safety of Everolimus in Combination Therapy,... | NCT00426556

ID	Type	Description	Link
2006-001596-37	EudraCT Number

Label	Type	Description	Intervention Names
Phase I - RAD001 5mg + PT, daily	Experimental	Daily dosing schedule of EPT = Paclitaxel & Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab.	Drug: Everolimus Drug: Trastuzumab Drug: Paclitaxel
Phase I - RAD001 10mg + PT, daily	Experimental	Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab	Drug: Everolimus Drug: Trastuzumab Drug: Paclitaxel
Phase I - RAD001 30mg + PT, weekly	Experimental	Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab.	Drug: Everolimus Drug: Trastuzumab Drug: Paclitaxel
Phase II - RAD001 10mg + PT, daily	Experimental	Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab	Drug: Everolimus Drug: Trastuzumab Drug: Paclitaxel

Name	Type	Description	Arm Group Labels	Other Names
Everolimus	Drug	Everolimus (RAD001) was supplied as tablets in 3 different dosage strengths, 2.5, 5, and 10 mg. The drug was packaged in blisters containing 10 tablets per blister. Blisters and packaging labels were compliant with local regulations and were printed in local language.

Measure	Description	Time Frame
Phase II: Overall Response Rate	The primary objective of this phase II study was to evaluate the efficacy of the dose level/regimen of everolimus recommended from the Phase I with trastuzumab and paclitaxel (PT) therapy in patients with HER2-overexpressing metastatic breast cancer whose disease progressed on/after trastuzumab mono-and/or combination therapy based on the evaluation of objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Objective response rate (ORR) was defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR). Only patients with measurable disease (the presence of at least one measurable lesion) at baseline were included in the study. CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.	every 8 - 9 weeks until disease progression or a new lesion is identified

Measure	Description	Time Frame
Phase I: Best Overall Response (BOR)	BOR was determined based on investigator assessment of overall lesion response using RECIST criteria guidelines. BOR = objective responses rate (ORR), disease control rate (DCR) or clinical benefit rate (CBR). ORR = (complete response (CR) or partial response(PR); DCR = (CR or PR or Stable disease (SD); CBR = (CR or PR or SD >= 24 weeks).CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for partial disease (PD). PD = At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Wilshire Oncology Medical Group La Verne		see Various Departments	California		United States
Compassionate Cancer Care Medical Group Dept.ofCCCMG

Label	URL
Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.	View source

ID	Title	Description
FG000	Phase I - RAD001 5mg + PT, Daily	Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
FG001	Phase I - RAD001 10mg + PT, Daily

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

Phase II: Overall Response Rate

The primary objective of this phase II study was to evaluate the efficacy of the dose level/regimen of everolimus recommended from the Phase I with trastuzumab and paclitaxel (PT) therapy in patients with HER2-overexpressing metastatic breast cancer whose disease progressed on/after trastuzumab mono-and/or combination therapy based on the evaluation of objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Objective response rate (ORR) was defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR). Only patients with measurable disease (the presence of at least one measurable lesion) at baseline were included in the study. CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.

The Full Analysis Set (FAS) consisted of all patients who received a least one dose of any one compound of the study treatment. Patients were analyzed according to the everolimus dose level to which they enrolled.

Posted

Number

Percentage of Participants

every 8 - 9 weeks until disease progression or a new lesion is identified

ID	Title	Description
OG000	Phase I - RAD001 5mg + PT, Daily	Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
OG001	Phase I - RAD001 10mg + PT, Daily	Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
OG002	Phase I - RAD001 30mg + PT, Weekly	Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab.
OG003	Phase II - RAD001 10mg + PT, Daily	Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Title

Denominators

Categories

Title	Measurements
	OG00321.8

Secondary

Phase I: Best Overall Response (BOR)

BOR was determined based on investigator assessment of overall lesion response using RECIST criteria guidelines. BOR = objective responses rate (ORR), disease control rate (DCR) or clinical benefit rate (CBR). ORR = (complete response (CR) or partial response(PR); DCR = (CR or PR or Stable disease (SD); CBR = (CR or PR or SD >= 24 weeks).CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for partial disease (PD). PD = At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.

Posted

Number

Percentage of Participants

every 8 - 9 weeks until disease progression or a new lesion is identified

ID	Title	Description
OG000	Phase I - RAD001 5mg + PT, Daily	Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
OG001	Phase I - RAD001 10mg + PT, Daily	Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab

Secondary

Phase II: Progression Free Survival (PFS)

PFS is defined as the time from start of treatment to the date of first documented progression or death due to any cause. If a patient has not had an event, PFS will be censored at the date of last adequate tumor assessment.

Posted

Median

95% Confidence Interval

Months

every 8 - 9 weeks until disease progression or a new lesion is identified

ID	Title	Description
OG000	Phase I - RAD001 5mg + PT, Daily	Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
OG001	Phase I - RAD001 10mg + PT, Daily	Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
OG002	Phase I - RAD001 30mg + PT, Weekly	Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab.
OG003

Secondary

Phase II: Overall Survival (OS)

Overall survival (OS) is defined as the time from start of treatment to the date of death due to any cause. If a patient is not known to have died, survival was censored at the last date of contact. OS was to be reported at extension and after 3-year follow-up. The Kaplan-Meier median was used to analyze the OS.

Posted

Median

95% Confidence Interval

Months

every 3 months until death

ID	Title	Description
OG000	Phase I - RAD001 5mg + PT, Daily	Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
OG001	Phase I - RAD001 10mg + PT, Daily	Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
OG002	Phase I - RAD001 30mg + PT, Weekly	Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG0031 affected55 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Cardio-respiratory arrest	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Cardiopulmonary failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Visual impairment	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Impaired gastric emptying	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Subileus	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
General physical health deterioration	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Bile duct stenosis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Hepatic failure	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Bronchopneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Clostridium difficile colitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Device related infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Endocarditis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Enterocolitis infectious	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Herpes zoster	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0022 affected10 at risk EG003
Sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Septic shock	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Skin infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
White blood cell count decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Cell death	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Monarthritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Metastatic pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Brain oedema	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Coma	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Grand mal convulsion	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Intracranial pressure increased	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Confusional state	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Alveolitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Tracheal obstruction extrinsic	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Angioedema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Skin haemorrhage	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Jugular vein thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Lymphoedema	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Superior vena cava syndrome	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0005 affected6 at risk EG0015 affected17 at risk EG0024 affected10 at risk EG00319 affected55 at risk
Anaemia macrocytic	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0019 affected17 at risk EG0022 affected10 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0017 affected17 at risk EG0025 affected10 at risk EG003
Microcytosis	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0004 affected6 at risk EG00112 affected17 at risk EG0025 affected10 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0013 affected17 at risk EG0020 affected10 at risk EG003
Arrhythmia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Palpitations	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Tachycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0013 affected17 at risk EG0020 affected10 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Diplopia	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Dry eye	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Eye inflammation	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Eye pain	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Lacrimation increased	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected6 at risk EG0013 affected17 at risk EG0022 affected10 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Aphthous stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0013 affected17 at risk EG0020 affected10 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0018 affected17 at risk EG0025 affected10 at risk EG003
Dental caries	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0004 affected6 at risk EG00111 affected17 at risk EG0027 affected10 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0022 affected10 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Gastrointestinal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Gastrointestinal toxicity	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0021 affected10 at risk EG003
Gingival hypertrophy	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Gingivitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected6 at risk EG0017 affected17 at risk EG0025 affected10 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Oral disorder	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0021 affected10 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected6 at risk EG00116 affected17 at risk EG0028 affected10 at risk EG003
Tooth loss	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0015 affected17 at risk EG0024 affected10 at risk EG003
Adverse drug reaction	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0004 affected6 at risk EG0018 affected17 at risk EG0026 affected10 at risk EG003
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Chills	General disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Face oedema	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Facial pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0014 affected17 at risk EG0023 affected10 at risk EG003
Gait disturbance	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0021 affected10 at risk EG003
General physical health deterioration	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Influenza like illness	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Injection site pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Oedema	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0020 affected10 at risk EG003
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG00111 affected17 at risk EG0023 affected10 at risk EG003
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0004 affected6 at risk EG0017 affected17 at risk EG0021 affected10 at risk EG003
Xerosis	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0020 affected10 at risk EG003
Cytolytic hepatitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Hepatic steatosis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Hepatomegaly	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0020 affected10 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Acute tonsillitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0020 affected10 at risk EG003
Candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Clostridial infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Cystitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0022 affected10 at risk EG003
Device related infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Ear infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Erysipelas	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Escherichia urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Folliculitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0014 affected17 at risk EG0021 affected10 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Genital herpes	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Helicobacter infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Herpes simplex	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Herpes zoster	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Localised infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Lymphangitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Oral herpes	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0013 affected17 at risk EG0020 affected10 at risk EG003
Oral infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Rhinitis	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected6 at risk EG0015 affected17 at risk EG0020 affected10 at risk EG003
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0013 affected17 at risk EG0020 affected10 at risk EG003
Skin infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Subcutaneous abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Tonsillitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0020 affected10 at risk EG003
Tooth abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Tooth infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0012 affected17 at risk EG0020 affected10 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0013 affected17 at risk EG0021 affected10 at risk EG003
Vaginal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Viral infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Vulvovaginal mycotic infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Wound infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Pubis fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Radiation pneumonitis	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0012 affected17 at risk EG0021 affected10 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0014 affected17 at risk EG0020 affected10 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Blood creatine phosphokinase MB increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Blood magnesium decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Blood phosphorus decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Blood potassium decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Carbon monoxide diffusing capacity decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Echography abnormal	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Ejection fraction decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Electrocardiogram abnormal	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Haemoglobin decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Transaminases increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Troponin I increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0013 affected17 at risk EG0022 affected10 at risk EG003
Weight increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0020 affected10 at risk EG003
White blood cell count decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0022 affected10 at risk EG003
Cell death	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0020 affected10 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0017 affected17 at risk EG0023 affected10 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Dyslipidaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0021 affected10 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0012 affected17 at risk EG0021 affected10 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0021 affected10 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0016 affected17 at risk EG0022 affected10 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0013 affected17 at risk EG0021 affected10 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0020 affected10 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0013 affected17 at risk EG0020 affected10 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0020 affected10 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0004 affected6 at risk EG0013 affected17 at risk EG0021 affected10 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0013 affected17 at risk EG0020 affected10 at risk EG003
Tendon pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Ear neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0013 affected17 at risk EG0020 affected10 at risk EG003
Dysaesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0020 affected10 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0018 affected17 at risk EG0023 affected10 at risk EG003
Horner's syndrome	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Hypokinesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0012 affected17 at risk EG0021 affected10 at risk EG003
Neurotoxicity	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0016 affected17 at risk EG0024 affected10 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0021 affected10 at risk EG003
Sciatica	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Sinus headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Somnolence	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Agitation	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Confusional state	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0014 affected17 at risk EG0022 affected10 at risk EG003
Mood altered	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Sleep disorder	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0021 affected10 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Breast pain	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Genital discomfort	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Metrorrhagia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0016 affected17 at risk EG0022 affected10 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0013 affected17 at risk EG0021 affected10 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0016 affected17 at risk EG0022 affected10 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected6 at risk EG00111 affected17 at risk EG0023 affected10 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Larynx irritation	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Obstructive airways disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0021 affected10 at risk EG003
Pharyngeal ulceration	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0020 affected10 at risk EG003
Tracheal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0004 affected6 at risk EG0016 affected17 at risk EG0025 affected10 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0013 affected17 at risk EG0021 affected10 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0003 affected6 at risk EG0012 affected17 at risk EG0022 affected10 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0012 affected17 at risk EG0020 affected10 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0013 affected17 at risk EG0022 affected10 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Nail toxicity	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Onycholysis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Onychomadesis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Pigmentation disorder	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0022 affected10 at risk EG003
Purpura	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected6 at risk EG0018 affected17 at risk EG0023 affected10 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Rash vesicular	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Skin irritation	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Skin mass	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Skin toxicity	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0020 affected10 at risk EG003
Arterial thrombosis limb	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected17 at risk EG0021 affected10 at risk EG003
Hot flush	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0020 affected10 at risk EG003
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0011 affected17 at risk EG0021 affected10 at risk EG003
Lymphoedema	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0013 affected17 at risk EG0021 affected10 at risk EG003

ID	Term
D001943	Breast Neoplasms
D009362	Neoplasm Metastasis

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D020123	Sirolimus
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D004224	Diterpenes
D013729	Terpenes

ID	Title	Description
BG000	Phase I - RAD001 5mg + PT, Daily	Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
BG001	Phase I - RAD001 10mg + PT, Daily	Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
BG002	Phase I - RAD001 30mg + PT, Weekly	Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab.
BG003	Phase II - RAD001 10mg + PT, Daily	Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
BG004	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase I - Everolimus 5mg Daily + PT	Phase I - Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab	3	6	6	6
EG001	Phase I - Everolimus 10mg Daily + PT	Phase I - Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab	6	17	17	17
EG002	Phase I - Everolimus 30mg Weekly + PT	Phase I - Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab	7	10	10	10
EG003	Phase II - Everolimus 10mg Daily + PT	Phase II - Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab	26	55	55	55