A Study of MM-121 in Combination With Chemotherapy Versus... | NCT02387216

Name	Class
Merrimack Pharmaceuticals	INDUSTRY

Label	Type	Description	Intervention Names
Arm A: Experimental Arm	Experimental	MM-121 in combination with Docetaxel	Drug: MM-121 Drug: Docetaxel
Arm B: Comparator Arm	Active Comparator	Docetaxel alone	Drug: Docetaxel

Name	Type	Description	Arm Group Labels	Other Names
MM-121	Drug	Investigational, fully human antibody targeting and inhibiting ErbB3	Arm A: Experimental Arm

Measure	Description	Time Frame
Progression Free Survival	Progression Free Survival is defined as the time from randomization to the first documented radiographical progression of disease using RECIST v.1.1, or death from any cause, whichever came first based on investigator assessment. Patients that do not experience progression or death at the time of analysis were to be progression censored at the date of last valid tumor assessment. Progression-free survival time distribution and median survival for each treatment group were analyzed using the Kaplan-Meier method. Tumor response was evaluated by the local radiologist according to RECIST version 1.1 to establish disease progression by CT or MRI.	Randomization until progression of disease or death due to any cause within 3 years,11 months (the study terminated prematurely)

Measure	Description	Time Frame
Overall Survival	Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause	From date of randomization until the date of death from any cause assessed upto 3 years,11 months (the study terminated prematurely)
Objective Response Rate

Name	Affiliation	Role
MM-121 Program Medical Director, MD	Merrimack Pharmaceuticals	Study Director

PubMed Identifier	Type	Citation	Retractions
30975923	Derived	Sequist LV, Gray JE, Harb WA, Lopez-Chavez A, Doebele RC, Modiano MR, Jackman DM, Baggstrom MQ, Atmaca A, Felip E, Provencio M, Cobo M, Adiwijaya B, Kuesters G, Kamoun WS, Andreas K, Pipas JM, Santillana S, Cho BC, Park K, Shepherd FA. Randomized Phase II Trial of Seribantumab in Combination with Erlotinib in Patients with EGFR Wild-Type Non-Small Cell Lung Cancer. Oncologist. 2019 Aug;24(8):1095-1102. doi: 10.1634/theoncologist.2018-0695. Epub 2019 Apr 11.

ID	Title	Description
FG000	Arm A (Experimental): MM-121 in Combination With Docetaxel	MM-121 (Seribantumab, a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): 3000 mg fixed dose intravenous (IV) on Day 1 of each 21-day cycle Docetaxel (approved chemotherapy treatment for non-small cell lung cancer (NSCLC)): 75 mg/m˄2 IV on Day 1 of each 21-day cycle

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 2, 2017	Sep 21, 2020

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

Progression Free Survival

Progression Free Survival is defined as the time from randomization to the first documented radiographical progression of disease using RECIST v.1.1, or death from any cause, whichever came first based on investigator assessment.

Patients that do not experience progression or death at the time of analysis were to be progression censored at the date of last valid tumor assessment. Progression-free survival time distribution and median survival for each treatment group were analyzed using the Kaplan-Meier method. Tumor response was evaluated by the local radiologist according to RECIST version 1.1 to establish disease progression by CT or MRI.

The Modified Intent-to-Treat (mITT) Population consisted of all randomized patients who received at least 1 dose of assigned therapy

Posted

Median

Inter-Quartile Range

months

Randomization until progression of disease or death due to any cause within 3 years,11 months (the study terminated prematurely)

ID	Title	Description
OG000	Arm A (Experimental): MM-121 in Combination With Docetaxel	MM-121 (Seribantumab, a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): 3000 mg fixed dose intravenous (IV) on Day 1 of each 21-day cycle Docetaxel (approved chemotherapy treatment for non-small cell lung cancer (NSCLC)): 75 mg/m˄2 IV on Day 1 of each 21-day cycle
OG001	Arm B (Comparator): Docetaxel Alone	Docetaxel (approved chemotherapy treatment for NSCLC): 75 mg/m˄2 IV on Day 1 of each 21-day cycle

Units	Counts
Participants	OG00071 OG00138

Title

Denominators

Categories

Title	Measurements
	OG0003.4(1.9 to 5.7) OG0014.1(2.7 to 6.3)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.2302		Hazard Ratio (HR)	1.382			2-Sided	95	0.813	2.350					Superiority

Secondary

Overall Survival

Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause

Modified Intent-to-Treat (ITT) population

Posted

Median

Inter-Quartile Range

months

From date of randomization until the date of death from any cause assessed upto 3 years,11 months (the study terminated prematurely)

ID	Title	Description
OG000	Arm A (Experimental): MM-121 in Combination With Docetaxel	MM-121 (Seribantumab, a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): 3000 mg fixed dose intravenous (IV) on Day 1 of each 21-day cycle Docetaxel (approved chemotherapy treatment for non-small cell lung cancer (NSCLC)): 75 mg/m˄2 IV on Day 1 of each 21-day cycle
OG001	Arm B (Comparator): Docetaxel Alone	Docetaxel (approved chemotherapy treatment for NSCLC): 75 mg/m˄2 IV on Day 1 of each 21-day cycle

Secondary

Objective Response Rate

Objective Response Rate (ORR) is defined as the proportion of patients a best overall response characterised as either a Complete Response (CR) or Partial Response (PR), as defined according to RECIST v1.1 guidelines, relative to the total number of evaluable patients.

Complete Response (CR) is defined as disappearance of all lesions and pathologic lymph nodes.

Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions

Modified Intent-to-Treat (ITT) population

Posted

Count of Participants

Participants

Randomization through end of study up to 3 years, 11 months (the study terminated prematurely)

ID	Title	Description
OG000	Arm A (Experimental): MM-121 in Combination With Docetaxel	MM-121 (Seribantumab, a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): 3000 mg fixed dose intravenous (IV) on Day 1 of each 21-day cycle Docetaxel (approved chemotherapy treatment for non-small cell lung cancer (NSCLC)): 75 mg/m˄2 IV on Day 1 of each 21-day cycle
OG001	Arm B (Comparator): Docetaxel Alone

Secondary

Time to Progression

Time to Progression (TTP) is defined as the time from the date of randomization to the date of objective tumor progression. In the actual analysis, duration of response (DOR) was analysed.

Modified Intent-to-Treat Population

Posted

Median

Inter-Quartile Range

months

Randomization to date of objective tumor progression up to 3 years, 11 months (the study terminated prematurely)

ID	Title	Description
OG000	Arm A (Experimental): MM-121 in Combination With Docetaxel	MM-121 (Seribantumab, a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): 3000 mg fixed dose intravenous (IV) on Day 1 of each 21-day cycle Docetaxel (approved chemotherapy treatment for non-small cell lung cancer (NSCLC)): 75 mg/m˄2 IV on Day 1 of each 21-day cycle
OG001	Arm B (Comparator): Docetaxel Alone	Docetaxel (approved chemotherapy treatment for NSCLC): 75 mg/m˄2 IV on Day 1 of each 21-day cycle

Secondary

Number of Participants With Treatment-emergent Adverse Events Reported With the Combination of MM-121 With Docetaxel Versus Docetaxel Alone

Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration

Safety Population

Posted

Number

participants

TEAEs were collected through the study completion (02 Jan 2019), up to 3 years, 11 months

ID	Title	Description
OG000	Arm A (Experimental): MM-121 in Combination With Docetaxel	MM-121 (Seribantumab, a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): 3000 mg fixed dose intravenous (IV) on Day 1 of each 21-day cycle Docetaxel (approved chemotherapy treatment for non-small cell lung cancer (NSCLC)): 75 mg/m˄2 IV on Day 1 of each 21-day cycle
OG001	Arm B (Comparator): Docetaxel Alone	Docetaxel (approved chemotherapy treatment for NSCLC): 75 mg/m˄2 IV on Day 1 of each 21-day cycle

Secondary

Pharmacokinetic (PK) Parameters of MM-121 in Combination With Docetaxel and Docetaxel When Given in Combination With MM-121.

Pharmacokinetic (PK) profile of MM-121 when given in combination with docetaxel, and of docetaxel when given in combination with MM-121. The maximum observed concentration (Cmax) were to be presented and calculated using non-compartmental analysis. Serum levels of MM-121 were to be measured at a central lab using an enzyme-linked immunosorbent assay.

The PK data were not collected for this abbreviated report. There was no pharmacokinetic data feasible for the analysis, and as such, no related analyses were performed. Hence, data could not be reported in the data table.

Posted

The study terminated prematurely after 3 years, 11 months (02 Jan 2019). PK evaluation were to be performed on samples obtained at Week 1 pre-dose and post-dose and at pre-dose at Cycle 2 and beyond to assess pre-treatment through concentrations of MM-121

ID	Title	Description
OG000	Arm A (Experimental): MM-121 in Combination With Docetaxel	MM-121 (Seribantumab, a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): 3000 mg fixed dose intravenous (IV) on Day 1 of each 21-day cycle Docetaxel (approved chemotherapy treatment for non-small cell lung cancer (NSCLC)): 75 mg/m˄2 IV on Day 1 of each 21-day cycle

Secondary

Percentage of Participants With Treatment-emergent Adverse Events Reported With the Combination of MM-121 With Docetaxel Versus Docetaxel Alone

Safety Population

Posted

Number

percentage of participants

TEAEs were collected through the study completion (02 Jan 2019), up to 3 years, 11 months

ID	Title	Description
OG000	Arm A (Experimental): MM-121 in Combination With Docetaxel	MM-121 (Seribantumab, a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): 3000 mg fixed dose intravenous (IV) on Day 1 of each 21-day cycle Docetaxel (approved chemotherapy treatment for non-small cell lung cancer (NSCLC)): 75 mg/m˄2 IV on Day 1 of each 21-day cycle
OG001	Arm B (Comparator): Docetaxel Alone	Docetaxel (approved chemotherapy treatment for NSCLC): 75 mg/m˄2 IV on Day 1 of each 21-day cycle

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00029 affected103 at risk EG00111 affected49 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00029 affected103 at risk EG00111 affected49 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0008 affected103 at risk EG0016 affected49 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0006 affected103 at risk EG0014 affected49 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0012 affected49 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0012 affected49 at risk
Tachycardia	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected103 at risk EG0010 affected49 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0012 affected49 at risk
Atrial flutter	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Cardio pulmonary failure	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Myocardial infarction	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Cardiac failure	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Hypothyroidism	Endocrine disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Cushingoid	Endocrine disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Lacrimation increased	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0007 affected103 at risk EG0014 affected49 at risk
Dry eye	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0010 affected49 at risk
Blepharospasm	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Eye irritation	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Vision blurred	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Eye pruritus	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Ocular hyperaemia	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00052 affected103 at risk EG00111 affected49 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00030 affected103 at risk EG00114 affected49 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00019 affected103 at risk EG0012 affected49 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00013 affected103 at risk EG0014 affected49 at risk
Constipation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0007 affected103 at risk EG0017 affected49 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0006 affected103 at risk EG0012 affected49 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0005 affected103 at risk EG0010 affected49 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected103 at risk EG0012 affected49 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0013 affected49 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0011 affected49 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0010 affected49 at risk
Colitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0013 affected49 at risk
Flatulence	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0010 affected49 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0013 affected49 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Odynophagia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Aphthous stomatitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0012 affected49 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Oral pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Anal fissure	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Anal haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Anal inflammation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Duodenitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Faeces discoloured	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Gastritis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Glossodynia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Glossitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Oral dysaesthesia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0012 affected49 at risk
Neutropenic colitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Rectal tenesmus	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Fatigue	General disorders	MedDRA 21.0	Systematic Assessment	EG00045 affected103 at risk EG00116 affected49 at risk
Asthenia	General disorders	MedDRA 21.0	Systematic Assessment	EG00028 affected103 at risk EG00111 affected49 at risk
Mucosal inflammation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00015 affected103 at risk EG0015 affected49 at risk
Pyrexia	General disorders	MedDRA 21.0	Systematic Assessment	EG00013 affected103 at risk EG0019 affected49 at risk
Pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0008 affected103 at risk EG0016 affected49 at risk
Oedema peripheral	General disorders	MedDRA 21.0	Systematic Assessment	EG0005 affected103 at risk EG0013 affected49 at risk
Chills	General disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected103 at risk EG0010 affected49 at risk
Chest pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0011 affected49 at risk
General physical health deterioration	General disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0011 affected49 at risk
Oedema	General disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0015 affected49 at risk
Non-cardiac chest pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Xerosis	General disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Ulcer	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Cyst	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Extravasation	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Hernia pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Hyperthermia	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Influenza like illness	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Infusion site reaction	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Gait disturbance	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Discomfort	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Local swelling	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Secretion discharge	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Seasonal allergy	Immune system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00012 affected103 at risk EG0016 affected49 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0008 affected103 at risk EG0010 affected49 at risk
Respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0006 affected103 at risk EG0013 affected49 at risk
Urinary tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0004 affected103 at risk EG0010 affected49 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0011 affected49 at risk
Oral candidiasis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0013 affected49 at risk
Sepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0012 affected49 at risk
Bronchitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0011 affected49 at risk
Candida infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0011 affected49 at risk
Conjunctivitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Herpes zoster	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Paronychia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0011 affected49 at risk
Oral herpes	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Fungal infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Influenza	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Rhinitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Appendicitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Diverticulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Furuncle	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Listeriosis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Lung abscess	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Mucosal infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Otitis media	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Septic shock	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Streptococcal bacteraemia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Tracheitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Vaginal infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Wound infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Nasopharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Pharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Sinusitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Device related infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Ear infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Laryngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Lymphangitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0012 affected49 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Incision site erythema	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Radiation pneumonitis	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Neutrophil count decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG00014 affected103 at risk EG0013 affected49 at risk
White blood cell count decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0008 affected103 at risk EG0011 affected49 at risk
Weight decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0007 affected103 at risk EG0014 affected49 at risk
Blood creatinine increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0011 affected49 at risk
Alanine aminotransferase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0011 affected49 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0010 affected49 at risk
Haemoglobin decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0011 affected49 at risk
Activated partial thromboplastin time prolonged	Investigations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0011 affected49 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Blood magnesium decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Lymphocyte count decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Platelet count decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Blood albumin decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Blood bilirubin increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Blood glucose increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Blood iron decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Blood phosphorus decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Blood sodium decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Breath sounds abnormal	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
International normalised ratio increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Lipase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Transaminases increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Urine analysis abnormal	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Weight increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Blood creatine increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
White blood cell count increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG00034 affected103 at risk EG0018 affected49 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0009 affected103 at risk EG0013 affected49 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0007 affected103 at risk EG0015 affected49 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected103 at risk EG0014 affected49 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected103 at risk EG0012 affected49 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected103 at risk EG0012 affected49 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected103 at risk EG0010 affected49 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0013 affected49 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0011 affected49 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Gout	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Hypovitaminosis	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Starvation	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0008 affected103 at risk EG0013 affected49 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0009 affected103 at risk EG0011 affected49 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0006 affected103 at risk EG0012 affected49 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0006 affected103 at risk EG0012 affected49 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected103 at risk EG0011 affected49 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0012 affected49 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0010 affected49 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0014 affected49 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0012 affected49 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Neck mass	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Seborrhoeic keratosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Dizziness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00012 affected103 at risk EG0011 affected49 at risk
Dysgeusia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0009 affected103 at risk EG0013 affected49 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0007 affected103 at risk EG0012 affected49 at risk
Paraesthesia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0006 affected103 at risk EG0011 affected49 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected103 at risk EG0013 affected49 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0010 affected49 at risk
Syncope	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0011 affected49 at risk
Hemiparesis	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Memory impairment	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Polyneuropathy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Neurotoxicity	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Presyncope	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Somnolence	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Amnesia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Lethargy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Paresis	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Restless legs syndrome	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Sciatica	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Sinus headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Spinal cord compression	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Vocal cord paralysis	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Ataxia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Cognitive disorder	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Motor dysfunction	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Encephalopathy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Confusional state	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0005 affected103 at risk EG0010 affected49 at risk
Insomnia	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0005 affected103 at risk EG0015 affected49 at risk
Anxiety	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0012 affected49 at risk
Delirium	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Agitation	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Depression	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Irritability	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Sleep disorder	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Anorexia nervosa	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Renal failure	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Haematuria	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Incontinence	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Renal venous congestion	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Urinary hesitation	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Urinary retention	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Hypertonic bladder	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Bartholin's cyst	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Vaginal inflammation	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Vulvovaginal pain	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Erectile dysfunction	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Breast pain	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Breast tenderness	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00020 affected103 at risk EG0019 affected49 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00012 affected103 at risk EG0016 affected49 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0009 affected103 at risk EG0010 affected49 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0006 affected103 at risk EG0012 affected49 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0005 affected103 at risk EG0011 affected49 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected103 at risk EG0010 affected49 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0011 affected49 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0011 affected49 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected103 at risk EG0010 affected49 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0011 affected49 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0010 affected49 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0012 affected49 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0011 affected49 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0011 affected49 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0011 affected49 at risk
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0011 affected49 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Obstructive airways disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Paranasal sinus hypersecretion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Catarrh	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Increased bronchial secretion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Rhinalgia	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00023 affected103 at risk EG00113 affected49 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00010 affected103 at risk EG0016 affected49 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0006 affected103 at risk EG0013 affected49 at risk
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0012 affected49 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0012 affected49 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0013 affected49 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0012 affected49 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Onycholysis	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Onychomadesis	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Nail toxicity	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Nail dystrophy	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Nail ridging	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0011 affected49 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Ingrowing nail	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Plantar erythema	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Hair colour changes	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0012 affected49 at risk
Dermatosis	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Onychalgia	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk
Pain management	Surgical and medical procedures	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Hypotension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0007 affected103 at risk EG0012 affected49 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected103 at risk EG0010 affected49 at risk
Hypertension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0011 affected49 at risk
Phlebitis	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected103 at risk EG0010 affected49 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0012 affected49 at risk
Embolism	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Haematoma	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Haemorrhage	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Hot flush	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Ischaemia	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Superior vena cava syndrome	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Flushing	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected103 at risk EG0010 affected49 at risk
Hypertensive crisis	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected103 at risk EG0011 affected49 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Tucson	Arizona	85715	United States

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
D000230	Adenocarcinoma
C565323	Fibromatosis, Gingival, 2

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes

ID	Title	Description
BG000	Arm A (Experimental): MM-121 in Combination With Docetaxel	MM-121 (Seribantumab, a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): 3000 mg fixed dose intravenous (IV) on Day 1 of each 21-day cycle Docetaxel (approved chemotherapy treatment for non-small cell lung cancer (NSCLC)): 75 mg/m˄2 IV on Day 1 of each 21-day cycle
BG001	Arm B (Comparator): Docetaxel Alone	Docetaxel (approved chemotherapy treatment for NSCLC): 75 mg/m˄2 IV on Day 1 of each 21-day cycle
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A (Experimental): MM-121 in Combination With Docetaxel	MM-121 (Seribantumab, a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): 3000 mg fixed dose intravenous (IV) on Day 1 of each 21-day cycle Docetaxel (approved chemotherapy treatment for non-small cell lung cancer (NSCLC)): 75 mg/m˄2 IV on Day 1 of each 21-day cycle	64	103	40	103	103	103
EG001	Arm B (Comparator): Docetaxel Alone	Docetaxel (approved chemotherapy treatment for NSCLC): 75 mg/m˄2 IV on Day 1 of each 21-day cycle	25	49	15	49	47	49