Phase 1b/2 Study of BKM120 Plus Trastuzumab in Patients W... | NCT01132664

ID	Type	Description	Link
2009-015417-46	EudraCT Number

Label	Type	Description	Intervention Names
HER2+ metastatic breast cancer	Experimental	Patients with HER2-overexpressing metastatic breast cancer, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab	Drug: BKM120 Drug: Trastuzumab
HER2+ metastatic breast cancer with BM	Experimental	Patients with HER2-overexpressing metastatic breast cancer and brain metastases, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab	Drug: BKM120 Drug: Trastuzumab Drug: Capecitabine

Name	Type	Description	Arm Group Labels	Other Names
BKM120	Drug	Buparlisib (BKM120) is the investigational drug. Burparlisib was supplied as 10 mg and 50 mg hard gelatin capsules. Buparlisib was dosed on a flat scale of mg/day and not adjusted to body weight or body surface area. Buparlisib capsules were packaged in high density polyethylene bottles with a plastic child resistant closure.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Dose Limiting Toxicity (DLT) - Phase l Only	Determination of the maximum tolerated dose (MTD) in the dose escalation part of the study was based upon the estimation of the probability of DLT in Cycle 1 in patients of the dose-determining set.	cycle 1 - 28 days
Overall Response Rate (ORR) - Phase ll	Objective response rate (ORR) was defined as the rate of patients with best overall response (BOR) equal to complete response (CR) or partial response (PR) according to RECIST 1.0 from the Investigators review. Per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 assessed of the disease status by imaging (i.e. CT/MRI): Complete Response (CR) = Disappearance of all tumor lesions; Partial Response (PR)= >=30% shrinkage of lesions; Overall Response (OR) = patients with CR and PR.	18 months

Secondary Outcomes

Measure	Description	Time Frame
Disease Control Rate (DCR) Based on Investigator Assessment- Phase l & ll	Disease control rate (DCR) = patients with complete response (CR), partial response (PR) or stable disease (SD) as per RECIST criteria. Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 assessed the disease status by imaging (i.e. CT/MRI): CR = disappearance of all tumor lesions; PR = >=30% shrinkage of lesions; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive 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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

World Health Organization (WHO) Performance Status of ≤ 2
Patients with HER2+ breast cancer by local laboratory testing (immunohistochemistry [IHC] 3+ staining or fluorescence in situ hybridization [FISH] confirmation for IHC 2+ and 1+)
Documented tumor resistance to trastuzumab:
- Recurrence while on trastuzumab or within 12 months since the last infusion for patients who received trastuzumab as adjuvant treatment
- Progression while on or within 4 weeks since the last infusion of trastuzumab for patients who received trastuzumab for metastatic disease.
Documented evidence of progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) on trastuzumab-based therapy defined as:
- Phase Ib: at any time before study entry
- Phase II: within 16 weeks before date of first dosing
Received at least 1 but no more than 4 prior anit-HER2 based regimens including at least 1 regimen containing trastuzumab (adjuvant or neo-adjuvant trastuzumab will be considered as one prior regimen). HER2 directed therapies are defined as comprising trastuzumab, lapatinib, and trastuzumab-DM1 (T-DM1) only.

• Phase II only: trastuzumab, T-DM1 or lapatinib must be part of the most recent line of therapy
Previous lines of cytotoxic chemotherapy:
- Phase Ib: no more than 4 lines of cytotoxic chemotherapy
- Phase II: no more than 3 lines of cytotoxic chemotherapy

Measurable disease:

Phase Ib: patient has at least one measurable lesion or non-measurable disease as defined per RECIST
Phase II: patient has at least one measureable lesion as defined per RECIST

|| Specific Inclusion Criteria for patients in BM cohorts:

Patient has evidence of progressing brain metastases and/or new metastatic brain lesion(s) without leptomeningeal disease.
Patient has received prior WBRT and/or SRS at at >28 and >/= 14 days, respectively, prior to starting study drug and the patient must have recovered from the side effects of the therapy
WHO performance status of \

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham/ Kirklin Clinic Univ AL - PI		Birmingham	Alabama	35294-0006	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Phase Ib - 50 mg	Patients in the phase Ib dose escalation cohort who received 50 mg of buparlisib - investigational drug
FG001	Phase Ib - 100mg	Patients in the phase Ib dose escalation cohort who received 100 mg of buparlisib - investigational drug

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

Dose Limiting Toxicity (DLT) - Phase l Only

Determination of the maximum tolerated dose (MTD) in the dose escalation part of the study was based upon the estimation of the probability of DLT in Cycle 1 in patients of the dose-determining set.

The Dose-determining set (DDS) for the determination of the MTD consisted of all patients from the safety set in the dose escalation phase who had met the minimum safety evaluation requirements and the minimum exposure criterion or had experienced DLT during Cycle 1 and were discontinued. MTD analysis was done only on the phase lb group.

Posted

Number

Participants

cycle 1 - 28 days

ID	Title	Description
OG000	Phase Ib - 50 mg	Patients in the phase Ib dose escalation cohort who received 50 mg of buparlisib - investigational drug
OG001	Phase Ib - 100mg	Patients in the phase Ib dose escalation cohort who received 100 mg of buparlisib - investigational drug
OG002	Phase II - 100mg	Patients in the phase II expansion + patients from phase Ib escalation included in phase II
OG003	BM Cohort - 80mg	Patients in the BM cohort who received 80 mg of buparlisib - investigational drug
OG004	BM Cohort - 100mg	Patients in the BM cohort who received 100 mg of buparlisib - investigational drug

Units	Counts
Participants	OG0004 OG00111 OG0020 OG003

Title

Denominators

Categories

Primary system orgran class (SOC) PT - grade 1

Title	Measurements
	OG0000 OG0010 OG0030 OG004

Primary

Overall Response Rate (ORR) - Phase ll

Objective response rate (ORR) was defined as the rate of patients with best overall response (BOR) equal to complete response (CR) or partial response (PR) according to RECIST 1.0 from the Investigators review.

Per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 assessed of the disease status by imaging (i.e. CT/MRI): Complete Response (CR) = Disappearance of all tumor lesions; Partial Response (PR)= >=30% shrinkage of lesions; Overall Response (OR) = patients with CR and PR.

The full analysis set (FAS) consisted of all patients who received at least one dose of study drug (buparlisib)

Posted

Number

Participants

18 months

ID	Title	Description
OG000	Phase Ib - 50 mg	Patients in the phase Ib dose escalation cohort who received 50 mg of buparlisib - investigational drug
OG001	Phase Ib - 100mg	Patients in the phase Ib dose escalation cohort who received 100 mg of buparlisib - investigational drug
OG002	Phase II - 100mg	Patients in the phase II expansion + patients from phase Ib escalation included in phase II
OG003

Secondary

Disease Control Rate (DCR) Based on Investigator Assessment- Phase l & ll

Disease control rate (DCR) = patients with complete response (CR), partial response (PR) or stable disease (SD) as per RECIST criteria.

Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 assessed the disease status by imaging (i.e. CT/MRI): CR = disappearance of all tumor lesions; PR = >=30% shrinkage of lesions; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive 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.

The full analysis set (FAS) consisted of all patients who received at least one dose of study drug (buparlisib).

CBR analysis was not done for the BM cohort population. DCR analysis was not done for the BM cohort population.

Posted

Number

Participants

18 months

ID	Title	Description
OG000	Phase Ib - 50 mg	Patients in the phase Ib dose escalation cohort who received 50 mg of buparlisib - investigational drug
OG001	Phase Ib - 100mg	Patients in the phase Ib dose escalation cohort who received 100 mg of buparlisib - investigational drug
OG002	Phase II - 100mg

Secondary

Clinical Benefit Rate (CBR) - Phase l & ll

CBR = patients with CR, PR or SD ≥ 24 weeks according to RECIST by the investigator.

Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 assessed the disease status by imaging (i.e. CT/MRI): CR = Disappearance of all tumor lesions; PR= >=30% shrinkage of lesions; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for 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.

The full analysis set (FAS) consisted of all patients who received at least one dose of study drug (buparlisib).

CBR analysis was not done for the BM cohort population.

Posted

Number

Participants

18 months

ID	Title	Description
OG000	Phase Ib - 50 mg	Patients in the phase Ib dose escalation cohort who received 50 mg of buparlisib - investigational drug
OG001	Phase Ib - 100mg	Patients in the phase Ib dose escalation cohort who received 100 mg of buparlisib - investigational drug
OG002	Phase II - 100mg	Patients in the phase II expansion + patients from phase Ib escalation included in phase II

Secondary

Progression Free Survival (PFS) - Based on Investigator Review Using Kaplan Meier - Phase l & ll

FAS consisted of all patients who received at least 1 dose of study drug (buparlisib). PFS analysis was not done for the BM cohort population. MTD/RP2D was not established due to premature termination of the study. In the phase ll portion of the study, PFS was analyzed only in patients with known PIK3 status, thus only 26/50 patients were analyzed.

Posted

Median

90% Confidence Interval

Months

18 months

ID	Title	Description
OG000	Phase Ib - 50 mg	Patients in the phase Ib dose escalation cohort who received 50 mg of buparlisib - investigational drug
OG001	Phase Ib - 100mg	Patients in the phase Ib dose escalation cohort who received 100 mg of buparlisib - investigational drug
OG002	Phase II - 100mg	Patients in the phase II expansion + patients from phase Ib escalation included in phase II
OG003	BM Cohort - 80mg	Patients in the BM cohort who received 80 mg of buparlisib - investigational drug

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG0030 affected3 at risk EG0040 affected6 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0023 affected50 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0022 affected50 at risk EG003
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0012 affected12 at risk EG0023 affected50 at risk EG003
General Physical Health Deterioration	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Oedema Peripheral	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Pain	General disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Systemic Inflammatory Response Syndrome	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Hepatic Failure	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Device Related Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0022 affected50 at risk EG003
Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Lobar Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Lower Respiratory Tract Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Lung Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Alanine Aminotransferase Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0022 affected50 at risk EG003
Aspartate Aminotransferase Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Bilirubin Conjugated Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Blood Bilirubin Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Diabetic Ketoacidosis	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Hypercreatininaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Bone Pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Muscular Weakness	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Musculoskeletal Stiffness	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Cerebral Haemorrhage	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Cerebrovascular Accident	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Convulsion	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Epilepsy	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Status Epilepticus	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Affective Disorder	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Confusional State	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Delirium	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Depressed Mood	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Mood Altered	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0022 affected50 at risk EG003
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0022 affected50 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Photosensitivity Reaction	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0022 affected50 at risk EG003
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0025 affected50 at risk EG0030 affected3 at risk EG0040 affected6 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Palpitations	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0023 affected50 at risk EG003
Dry Eye	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0012 affected12 at risk EG0022 affected50 at risk EG003
Extraocular Muscle Paresis	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Eye Irritation	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Eye Pain	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Ocular Hyperaemia	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Photophobia	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Vision Blurred	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Visual Impairment	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Abdominal Distension	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Abdominal Pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0013 affected12 at risk EG0027 affected50 at risk EG003
Abdominal Pain Lower	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0012 affected12 at risk EG0025 affected50 at risk EG003
Anal Fissure	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Aphthous Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0023 affected50 at risk EG003
Cheilitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0011 affected12 at risk EG0026 affected50 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0015 affected12 at risk EG00225 affected50 at risk EG003
Dry Mouth	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0022 affected50 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0026 affected50 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0023 affected50 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0020 affected50 at risk EG003
Gastrooesophageal Reflux Disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0023 affected50 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0020 affected50 at risk EG003
Haemorrhoids Thrombosed	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Lip Ulceration	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Mouth Ulceration	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0023 affected50 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected5 at risk EG0012 affected12 at risk EG00224 affected50 at risk EG003
Pigmentation Lip	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0014 affected12 at risk EG00212 affected50 at risk EG003
Tongue Discolouration	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Tooth Disorder	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected5 at risk EG0012 affected12 at risk EG00213 affected50 at risk EG003
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0016 affected12 at risk EG00213 affected50 at risk EG003
Chest Pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Face Oedema	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG00216 affected50 at risk EG003
Gait Disturbance	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Injection Site Reaction	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Mucosal Dryness	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0012 affected12 at risk EG0021 affected50 at risk EG003
Mucosal Inflammation	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Non-Cardiac Chest Pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0027 affected50 at risk EG003
Oedema Peripheral	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0023 affected50 at risk EG003
Pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0020 affected50 at risk EG003
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0025 affected50 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Cystitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Device Related Sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Ear Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Eczema Infected	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Furuncle	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0020 affected50 at risk EG003
Herpes Zoster	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0022 affected50 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Oral Herpes	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0023 affected50 at risk EG003
Paronychia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0022 affected50 at risk EG003
Pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Urinary Tract Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0022 affected50 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Rib Fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Spinal Fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Tooth Fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Vaginal Laceration	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0020 affected50 at risk EG003
Wound Complication	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Alanine Aminotransferase Decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Alanine Aminotransferase Increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0014 affected12 at risk EG00218 affected50 at risk EG003
Amylase Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Aspartate Aminotransferase Increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0014 affected12 at risk EG00217 affected50 at risk EG003
Blood Alkaline Phosphatase Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0012 affected12 at risk EG0027 affected50 at risk EG003
Blood Bilirubin Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0023 affected50 at risk EG003
Blood Calcium Decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Blood Cholesterol Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Blood Creatine Phosphokinase Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Blood Creatinine Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0022 affected50 at risk EG003
Blood Glucose Decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Blood Glucose Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0022 affected50 at risk EG003
Blood Thyroid Stimulating Hormone Increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Blood Uric Acid Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
C-Reactive Protein Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Eastern Cooperative Oncology Group Performance Status Worsened	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0023 affected50 at risk EG003
Ejection Fraction Decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0022 affected50 at risk EG003
Gamma-Glutamyltransferase Increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0013 affected12 at risk EG0027 affected50 at risk EG003
Glycosylated Haemoglobin Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Haemoglobin Decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Insulin C-Peptide Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Lipase Increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Liver Function Test Abnormal	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Low Density Lipoprotein Increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Lymphocyte Count Decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Protein Urine Present	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Weight Decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0011 affected12 at risk EG0027 affected50 at risk EG003
White Blood Cell Count Decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Decreased Appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0011 affected12 at risk EG00218 affected50 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0022 affected50 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected5 at risk EG0015 affected12 at risk EG00215 affected50 at risk EG003
Hyperphagia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0022 affected50 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0023 affected50 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0023 affected50 at risk EG003
Increased Appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0023 affected50 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0012 affected12 at risk EG0026 affected50 at risk EG003
Bone Pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0023 affected50 at risk EG003
Muscle Spasms	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0024 affected50 at risk EG003
Muscular Weakness	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Musculoskeletal Chest Pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0012 affected12 at risk EG0022 affected50 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Pain In Extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0025 affected50 at risk EG003
Tumour Pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Balance Disorder	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0025 affected50 at risk EG003
Cluster Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0026 affected50 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0011 affected12 at risk EG0027 affected50 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0011 affected12 at risk EG00211 affected50 at risk EG003
Memory Impairment	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0022 affected50 at risk EG003
Neuropathy Peripheral	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0011 affected12 at risk EG0023 affected50 at risk EG003
Peripheral Sensory Neuropathy	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Somnolence	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0022 affected50 at risk EG003
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Tremor	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0023 affected50 at risk EG003
Affective Disorder	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0013 affected12 at risk EG0025 affected50 at risk EG003
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG00211 affected50 at risk EG003
Binge Eating	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Delirium	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Depressed Mood	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0023 affected50 at risk EG003
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0002 affected5 at risk EG0011 affected12 at risk EG0028 affected50 at risk EG003
Initial Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0012 affected12 at risk EG0026 affected50 at risk EG003
Irritability	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Mood Altered	Psychiatric disorders	MedDRA	Systematic Assessment	EG0003 affected5 at risk EG0014 affected12 at risk EG0027 affected50 at risk EG003
Nervousness	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Restlessness	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Suicidal Ideation	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Chromaturia	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Micturition Urgency	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Breast Pain	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Vulvovaginal Discomfort	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0014 affected12 at risk EG00215 affected50 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0026 affected50 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Interstitial Lung Disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0024 affected50 at risk EG003
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0021 affected50 at risk EG003
Pleuritic Pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Productive Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Respiratory Disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Blister	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Dermatitis Acneiform	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Dry Skin	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0013 affected12 at risk EG0026 affected50 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0023 affected50 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0023 affected50 at risk EG003
Nail Disorder	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0020 affected50 at risk EG003
Night Sweats	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Palmar-Plantar Erythrodysaesthesia Syndrome	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0022 affected50 at risk EG003
Photosensitivity Reaction	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected5 at risk EG0013 affected12 at risk EG0027 affected50 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0016 affected12 at risk EG00216 affected50 at risk EG003
Rash Generalised	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0023 affected50 at risk EG003
Rash Pruritic	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0024 affected50 at risk EG003
Skin Discolouration	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Skin Exfoliation	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected12 at risk EG0021 affected50 at risk EG003
Skin Lesion	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Swelling Face	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0013 affected12 at risk EG0026 affected50 at risk EG003
Orthostatic Hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected12 at risk EG0020 affected50 at risk EG003

ID	Term
D001943	Breast Neoplasms
D001932	Brain Neoplasms

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D016543	Central Nervous System Neoplasms
D009423	Nervous System Neoplasms
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases

ID	Term
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
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D005472	Fluorouracil
D014498	Uracil
D011744	Pyrimidinones
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides

ID	Title	Description
BG000	Phase Ib - 50 mg	Patients in the phase Ib dose escalation cohort who received 50 mg of buparlisib - investigational drug
BG001	Phase Ib - 100mg	Patients in the phase Ib dose escalation cohort who received 100 mg of buparlisib - investigational drug
BG002	Phase II - 100mg	Patients in the phase II only expansion cohort who received 100 mg of buparlisib - investigational drug
BG003	BM Cohort - 80mg	Patients in the BM cohort who received 80 mg of buparlisib - investigational drug
BG004	BM Cohort - 100mg	Patients in the BM cohort who received 100 mg of buparlisib - investigational drug
BG005	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 Ib Dose Escalation 50 mg/Day	Patients in the phase Ib dose escalation cohort who received 50 mg of buparlisib - investigational drug.	2	5	5	5
EG001	Phase Ib Dose Escalation 100 mg/Day	Patients in the phase Ib dose escalation cohort who received 100 mg of buparlisib - investigational drug	2	12	12	12
EG002	Phase II Dose Expansion 100 mg/Day	Patients in the phase II expansion + patients from phase Ib dose escalation who received 100 mg/day of buparlisib - investigational drug	17	50	50	50
EG003	BM Cohort 80 mg/Day	Patients in the BM cohort who received 80 mg of buparlisib - investigational drug	2	3	3	3
EG004	BM Cohort 100 mg/Day	Patients in the BM cohort who received 100 mg of buparlisib - investigational drug	4	6	6	6

ID	Term
C571178	NVP-BKM120
D000068878	Trastuzumab
D000069287	Capecitabine