LUME-Lung 1: BIBF 1120 Plus Docetaxel as Compared to Plac... | NCT00805194

NCT00805194

ID	Type	Description	Link
2007-004803-36	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
BIBF 1120 plus docetaxel	Experimental	BIBF 1120 2 times daily along with standard therapy of docetaxel	Drug: BIBF 1120 plus docetaxel
Placebo plus docetaxel	Placebo Comparator	Placebo matching BIBF 1120 2 times daily along with standard therapy of docetaxel	Drug: placebo plus docetaxel

Name	Type	Description	Arm Group Labels	Other Names
placebo plus docetaxel	Drug	placebo matching BIBF 1120 2 times daily along with standard therapy of docetaxel	Placebo plus docetaxel

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression Free Survival (PFS) as Assessed by Central Independent Review	Progression Free Survival (PFS) as assessed by central independent review according to the modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) . Progression free survival (PFS) is defined as the duration of time from date of randomisation to date of progression or death (whatever occurs earlier). Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.	From randomisation until cut-off date 2 November 2010 (when 713 PFS events were observed)

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (Key Secondary Endpoint)	Overall Survival (OS) defined as the duration from randomisation to death (irrespective of the reason of death). Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve. A fixed-sequence-testing was implemented for key secondary endpoint if both the primary and the follow-up analysis showed a treatment benefit (P<0.05) of nintedanib over placebo. In this case, the OS would be tested using hierarchical testing of statistical hypotheses in (1) patients with adenocarcinoma and <9 months since start of first-line therapy, (2) patients with adenocarcinoma, and (3) all patients. Each hypothesis could be only tested at the pre-specified alpha level if the previous null hypothesis in the testing sequence had been.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

male or female patient aged 18 years or older;
histologically or cytologically confirmed, locally advanced and/or metastatic NSCLC of stage IIIB or IV or recurrent NSCLC;
relapse or failure of one first line prior chemotherapy;
at least one target tumour lesion that has not been irradiated within the past three months and that can accurately be measured ;
life expectancy of at least three months;
Eastern Cooperative Oncology group (ECOG) score of 0 or 1;
patient has given written informed consent

Exclusion criteria:

more than one prior chemotherapy regimen for advanced and/or metastatic or recurrent NSCLC;
more than one chemotherapy treatment regimen (either neoadjuvant or adjuvant or neoadjuvant plus adjuvant) prior to first line chemotherapy;
previous therapy with other VEGFR inhibitors (other than bevacizumab) or docetaxel for treatment of NSCLC;
persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy;
treatment with other investigational drugs or other anti-cancer therapy or treatment in another clinical trial within the past four weeks before start of - therapy or concomitantly with this trial ;
radiotherapy (except extremities and brain) within the past three months prior to baseline imaging;
active brain metastases or leptomeningeal disease;
radiographic evidence of cavitary or necrotic tumours;
centrally located tumours with radiographic evidence (CT or MRI) of local invasion of major blood vessels;
history of clinically significant haemoptysis within the past 3 months;
therapeutic anticoagulation (except low dose heparin) or antiplatelet therapy;
history of major thrombotic or clinically relevant major bleeding event in the past 6 months;
known inherited predisposition to bleeding or thrombosis;
significant cardiovascular diseases ;
inadequate safety laboratory parameters;
significant weight loss (> 10 %) within the past 6 weeks;
current peripheral neuropathy greater than CTCAE grade 2 except due to trauma;
preexisting ascites and/or clinically significant pleural effusion;
major injuries and/or surgery within the past ten days prior to randomisation with incomplete wound healing;
serious infections requiring systemic antibiotic therapy;
decompensated diabetes mellitus or other contraindication to high dose corticosteroid therapy;
gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug;
active or chronic hepatitis C and/or B infection;
serious illness or concomitant non-oncological disease or laboratory abnormality that may increase the risk associated with study participation or study drug administration;
patients who are sexually active and unwilling to use a medically acceptable method of contraception during the trial and for at least twelve months after end of active therapy;
pregnancy or breast feeding;
psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule;
patients unable to comply with the protocol;
active alcohol or drug abuse;
other malignancy within the past three years other than basal cell skin cancer, or carcinoma in situ of the cervix;
any contraindications for therapy with docetaxel;
history of severe hypersensitivity reactions to docetaxel or other drugs formulated with polysorbate 80 (Tween 80);
hypersensitivity to BIBF 1120 and/or the excipients of the trial drugs;
hypersensitivity to contrast media

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
LKH-Univ. Hospital Graz		Graz		8036	Austria
KH St. Vinzenz, Zams, Int. Abtlg.

PubMed Identifier	Type	Citation	Retractions
28702806	Derived	Gottfried M, Bennouna J, Bondarenko I, Douillard JY, Heigener DF, Krzakowski M, Mellemgaard A, Novello S, Orlov S, Summers Y, von Pawel J, Stohr J, Kaiser R, Reck M. Efficacy and Safety of Nintedanib Plus Docetaxel in Patients with Advanced Lung Adenocarcinoma: Complementary and Exploratory Analyses of the Phase III LUME-Lung 1 Study. Target Oncol. 2017 Aug;12(4):475-485. doi: 10.1007/s11523-017-0517-2.
24411639

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Nintedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
FG001	Placebo Plus Docetaxel

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0003.4(1.5 to 5.7) OG0012.7(1.4 to 4.6)

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	HR, Confidence Interval (CI) and p-value obtained from the proportional hazards model stratified by baseline ECOG PS (0 vs 1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)	Regression, Cox		0.0019		Hazard Ratio (HR)	0.79			2-Sided	95	0.68	0.92			Hazard Ratio (HR) below 1 favors nintedanib		Superiority or Other

Secondary

Overall Survival (Key Secondary Endpoint)

Overall Survival (OS) defined as the duration from randomisation to death (irrespective of the reason of death). Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

A fixed-sequence-testing was implemented for key secondary endpoint if both the primary and the follow-up analysis showed a treatment benefit (P<0.05) of nintedanib over placebo. In this case, the OS would be tested using hierarchical testing of statistical hypotheses in (1) patients with adenocarcinoma and <9 months since start of first-line therapy, (2) patients with adenocarcinoma, and (3) all patients. Each hypothesis could be only tested at the pre-specified alpha level if the previous null hypothesis in the testing sequence had been.

Randomised Set

Posted

Median

Inter-Quartile Range

months

From randomisation until cut-off date 15 February 2013 (approximately 48 months or 1151 deaths among all patients )

ID	Title	Description
OG000	Nintedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
OG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Secondary

Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Central Independent Review

Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by central independent review according to the modified RECIST (version 1.0) criteria.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Randomised Set

Posted

Median

Inter-Quartile Range

months

From randomisation until cut-off date 15 February 2013

ID	Title	Description
OG000	Nintedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
OG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Units	Counts
Participants

Secondary

Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Investigator

Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by investigator according to the modified RECIST (version 1.0) criteria.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Randomised Set

Posted

Median

Inter-Quartile Range

months

From randomisation until cut-off date 15 February 2013

ID	Title	Description
OG000	Nintedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
OG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Units	Counts
Participants

Secondary

Objective Tumour Response

Confirmed objective response is defined as confirmed Complete Response (CR) and Partial Response (PR) and evaluated according to the modified RECIST criteria version 1.0.

As per RECIST v1.0, Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Randomised Set

Posted

Number

% of participants

From randomisation until cut-off date 15 February 2013

ID	Title	Description
OG000	Nintedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
OG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Units	Counts
Participants

Secondary

Duration of Confirmed Objective Tumour Response

The duration of objective response is the time from first documented (CR) or (PR) to the time of progression or death and evaluated according to the modified RECIST criteria version 1.0.

As per RECIST v1.0, Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Randomised Set

Posted

Median

Inter-Quartile Range

months

From randomisation until cut-off date 15 February 2013

ID	Title	Description
OG000	Nintedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
OG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Units

Secondary

Time to Confirmed Objective Tumour Response

Time to confirmed objective response is defined as time from randomisation to the date of first documented (CR) or (PR) and evaluated according to the modified RECIST criteria version 1.0.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Randomised Set

Posted

Median

Inter-Quartile Range

months

From randomisation until cut-off date 15 February 2013

ID	Title	Description
OG000	Nintedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
OG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Units	Counts
Participants

Secondary

Disease Control

Disease control was defined as a best overall response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) and evaluated according to the modified RECIST criteria version 1.0.

As per RECIST v1.0 for target lesions : Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Randomised Set

Posted

Number

% of participants

From randomisation until cut-off date 15 February 2013

ID	Title	Description
OG000	Nintedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
OG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 (with dose reduction to 60 mg/m2 if required) once every 3 weeks administered via intravenous infusion over 1 hour (h).

Secondary

Duration of Disease Control

The duration of disease control was defined as the time from randomisation to the date of disease progression or death (which ever occurs first) for patients with disease control.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Randomised Set

Posted

Median

Inter-Quartile Range

months

From randomisation until cut-off date 15 February 2013

ID	Title	Description
OG000	Nintedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
OG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Units	Counts
Participants

Secondary

Change From Baseline in Tumour Size

Percentage change from baseline in tumour size is defined as decrease in the sum of the longest diameter of the target lesion.

Presented means are in fact adjusted best means percentage changes generated from ANOVA model adjusted for baseline ECOG PS (0 vs. 1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Randomised Set

Posted

Mean

95% Confidence Interval

percentage of change in tumor size in mm

From randomisation until cut-off date 15 February 2013

ID	Title	Description
OG000	Nintedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
OG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Units	Counts

Secondary

Clinical Improvement

Clinical improvement was defined as the time from randomisation to deterioration in body weight and/or Eastern Cooperative Oncology group performance score (ECOG PS) whichever occurred first.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Randomised set

Posted

Median

Inter-Quartile Range

months

From randomisation until cut-off date 15 February 2013

ID	Title	Description
OG000	Nitedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
OG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Units	Counts
Participants	OG000

Secondary

Quality of Life (QoL)

Quality of life (QoL) was measured by standardised questionnaires (Health Status Self-Assessment Questionnaire (EQ-5D), EORTC Quality of life questionnaire - Core 30 (EORTC QLQ-C30), Quality of life questionnaire - lung cancer module (EORTC QLQ-LC13). The EORTC QLQ-C30 comprises of 30 questions, using both multi-item scales and single-item measures. EORTC LC-13 comprises of 13 questions incorporating 1 multi-item scale and a series of single items.

The following were the main points of interest:

Time to deterioration of cough (EORTC QLQ-LC13 question 1), Time to deterioration of dyspnoea (QLQ-LC13, composite of questions 3 to 5), Time to deterioration of pain (QLQ- C30, composite of questions 9 and 19).

Time to deterioration of cough, dyspnoea and pain was defined as the time to a 10-point increase from the baseline score.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve

Randomised set

Posted

Median

Inter-Quartile Range

months

From randomisation until cut-off date 15 February 2013

ID	Title	Description
OG000	Nitedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
OG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Secondary

Dose Normalised Predose Plasma Concentration at Steady State (Cpre,ss,Norm) of Nintedanib and of Its Metabolites BIBF 1202 and BIBF 1202 Glucuronide

Geometric mean of dose normalised predose plasma concentration (Cpre,ss,norm) of nintedanib and of its metabolites BIBF 1202 and BIBF 1202 glucuronide evaluated at steady state based on course 2 and 3. If only one value was available and valid, then this value was used for calculation of Cpre,ss,norm.

Pharmacokinetic set- all patients in the treated set who were documented to have received at least 1 dose of nintedanib and who had at least 1 valid drug plasma concentration available

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL/mg

Before the administration of nintedanib or placebo and between a window of 30 mins to an hour after administration of trial drug during Course 2 and between 1 and 3 hours after administration of trial drug during Course 3

ID	Title	Description
OG000	Nitedanib 200 mg Bid Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
OG001	Nintedanib 150 Bid mg Plus Docetaxel	Nintedanib 150 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Secondary

Incidence and Intensity of Adverse Events

Incidence and intensity of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The worst CTCAE grade per patient is reported and MedDRA version 15.1 used.

Serious signs and symptoms of progressive disease were reported as an adverse event in analysis of this endpoint.

Treated set- all randomised patients who were documented to have taken at least 1 dose of study medication . Patients were allocated to the treatment groups according to the treatment actually received.

Posted

Number

% of participants

From the first drug administration until 28 days after the last drug administration, up to 42 months

ID	Title	Description
OG000	Nitedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
OG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).

Units	Counts

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0016 affected655 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 15.1	Systematic Assessment	EG00030 affected652 at risk EG00119 affected655 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 15.1	Systematic Assessment	EG00021 affected652 at risk EG00121 affected655 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0010 affected655 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0012 affected655 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Angina pectoris	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0005 affected652 at risk EG0012 affected655 at risk
Atrial flutter	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Atrioventricular block second degree	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Cardiac arrest	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Cardiac failure	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Coronary artery disease	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Myocardial infarction	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0013 affected655 at risk
Pericardial effusion	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0004 affected652 at risk EG0010 affected655 at risk
Pericarditis	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Tachyarrhythmia	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0010 affected655 at risk
Ventricular arrhythmia	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0012 affected655 at risk
Diplopia	Eye disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0014 affected655 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0012 affected655 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG00016 affected652 at risk EG00113 affected655 at risk
Diverticulum intestinal	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0012 affected655 at risk
Enteritis	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Gastric perforation	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Gastritis erosive	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Gastrointestinal necrosis	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Haematochezia	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Nausea	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Neutropenic colitis	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0010 affected655 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0013 affected655 at risk
Vomiting	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0008 affected652 at risk EG0017 affected655 at risk
Asthenia	General disorders	MedDRA 15.1	Systematic Assessment	EG0007 affected652 at risk EG0014 affected655 at risk
Chest discomfort	General disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Chest pain	General disorders	MedDRA 15.1	Systematic Assessment	EG0007 affected652 at risk EG0018 affected655 at risk
Condition aggravated	General disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Death	General disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0011 affected655 at risk
Device occlusion	General disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Extravasation	General disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Fatigue	General disorders	MedDRA 15.1	Systematic Assessment	EG0007 affected652 at risk EG0011 affected655 at risk
Feeling abnormal	General disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
General physical health deterioration	General disorders	MedDRA 15.1	Systematic Assessment	EG00011 affected652 at risk EG0018 affected655 at risk
Malaise	General disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Mucosal inflammation	General disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Multi-organ failure	General disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0011 affected655 at risk
Oedema peripheral	General disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Organ failure	General disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Pain	General disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Performance status decreased	General disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Pyrexia	General disorders	MedDRA 15.1	Systematic Assessment	EG0007 affected652 at risk EG0019 affected655 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Cholecystocholangitis	Hepatobiliary disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Cholestasis	Hepatobiliary disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0011 affected655 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0012 affected655 at risk
Hypersensitivity	Immune system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0013 affected655 at risk
Abscess rupture	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Appendicitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Bronchitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0014 affected655 at risk
Bronchopneumonia	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Cellulitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Empyema	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Erysipelas	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Febrile infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Folliculitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Gastroenteritis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0012 affected655 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
H1N1 influenza	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0012 affected655 at risk
Infectious pleural effusion	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0011 affected655 at risk
Influenza	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Laryngitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0004 affected652 at risk EG0013 affected655 at risk
Lung abscess	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Lung infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Neutropenic infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Neutropenic sepsis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Opportunistic infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Oral candidiasis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Perirectal abscess	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Pharyngitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0010 affected655 at risk
Pneumonia	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG00017 affected652 at risk EG00126 affected655 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Respiratory tract infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0013 affected655 at risk
Respiratory tract infection bacterial	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Sepsis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0007 affected652 at risk EG0013 affected655 at risk
Septic shock	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0010 affected655 at risk
Streptococcal infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Tuberculosis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0013 affected655 at risk
Urinary tract infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Acetabulum fracture	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Alanine aminotransferase increased	Investigations	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0010 affected655 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0010 affected655 at risk
Blood creatinine increased	Investigations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Haemoglobin decreased	Investigations	MedDRA 15.1	Systematic Assessment	EG0003 affected652 at risk EG0012 affected655 at risk
Hepatic enzyme increased	Investigations	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Liver function test abnormal	Investigations	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Neutrophil count decreased	Investigations	MedDRA 15.1	Systematic Assessment	EG0006 affected652 at risk EG0013 affected655 at risk
Weight decreased	Investigations	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
White blood cell count decreased	Investigations	MedDRA 15.1	Systematic Assessment	EG0003 affected652 at risk EG0012 affected655 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG0005 affected652 at risk EG0011 affected655 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG0004 affected652 at risk EG0010 affected655 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0012 affected655 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Haemarthrosis	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0010 affected655 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Hepatic cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG00025 affected652 at risk EG00117 affected655 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0012 affected655 at risk
Metastases to chest wall	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Metastases to kidney	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0003 affected652 at risk EG0010 affected655 at risk
Metastases to skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Metastatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Metastatic pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Tumour necrosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Aphasia	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Brain oedema	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Cerebral infarction	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0012 affected655 at risk
Cognitive disorder	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Coma	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Convulsion	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0004 affected652 at risk EG0010 affected655 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Diplegia	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Dizziness	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Encephalopathy	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Epiduritis	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Facial paresis	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Headache	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Hemiplegia	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Intracranial pressure increased	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Lethargy	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Loss of consciousness	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0010 affected655 at risk
Monoparesis	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Nervous system disorder	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Neuralgia	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Paraesthesia	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Paraparesis	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Restless legs syndrome	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Spinal cord compression	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0012 affected655 at risk
Syncope	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Confusional state	Psychiatric disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0012 affected655 at risk
Depression	Psychiatric disorders	MedDRA 15.1	Systematic Assessment	EG0004 affected652 at risk EG0010 affected655 at risk
Disorientation	Psychiatric disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0013 affected655 at risk
Mental disorder due to a general medical condition	Psychiatric disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Panic attack	Psychiatric disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Personality change	Psychiatric disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Psychotic disorder	Psychiatric disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Bladder perforation	Renal and urinary disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Haematuria	Renal and urinary disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Urinary retention	Renal and urinary disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0012 affected655 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0010 affected655 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0003 affected652 at risk EG0011 affected655 at risk
Alveolitis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected652 at risk EG0011 affected655 at risk
Bronchial haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Bronchial secretion retention	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Bronchostenosis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0003 affected652 at risk EG0012 affected655 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG00024 affected652 at risk EG00130 affected655 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0006 affected652 at risk EG0017 affected655 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Obstructive airways disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0008 affected652 at risk EG0018 affected655 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0003 affected652 at risk EG0011 affected655 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0004 affected652 at risk EG0016 affected655 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0005 affected652 at risk EG0013 affected655 at risk
Respiratory depression	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0008 affected652 at risk EG0012 affected655 at risk
Stridor	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Tracheal stenosis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Circulatory collapse	Vascular disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 15.1	Systematic Assessment	EG0003 affected652 at risk EG0011 affected655 at risk
Haemorrhage	Vascular disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0012 affected655 at risk
Hypotension	Vascular disorders	MedDRA 15.1	Systematic Assessment	EG0003 affected652 at risk EG0011 affected655 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Subclavian artery thrombosis	Vascular disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Superior vena cava syndrome	Vascular disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0011 affected655 at risk
Thrombosis	Vascular disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected652 at risk EG0011 affected655 at risk
Venous thrombosis	Vascular disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk
Venous thrombosis limb	Vascular disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected652 at risk EG0010 affected655 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 15.1	Systematic Assessment	EG00033 affected652 at risk EG00143 affected655 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 15.1	Systematic Assessment	EG00069 affected652 at risk EG00173 affected655 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG00035 affected652 at risk EG00137 affected655 at risk
Constipation	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG00035 affected652 at risk EG00176 affected655 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG000260 affected652 at risk EG001130 affected655 at risk
Nausea	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG000158 affected652 at risk EG001117 affected655 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG00062 affected652 at risk EG00154 affected655 at risk
Vomiting	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG000102 affected652 at risk EG00154 affected655 at risk
Asthenia	General disorders	MedDRA 15.1	Systematic Assessment	EG00051 affected652 at risk EG00160 affected655 at risk
Chest pain	General disorders	MedDRA 15.1	Systematic Assessment	EG00049 affected652 at risk EG00154 affected655 at risk
Fatigue	General disorders	MedDRA 15.1	Systematic Assessment	EG000191 affected652 at risk EG001175 affected655 at risk
Oedema peripheral	General disorders	MedDRA 15.1	Systematic Assessment	EG00035 affected652 at risk EG00142 affected655 at risk
Pyrexia	General disorders	MedDRA 15.1	Systematic Assessment	EG00076 affected652 at risk EG00189 affected655 at risk
Alanine aminotransferase increased	Investigations	MedDRA 15.1	Systematic Assessment	EG000184 affected652 at risk EG00155 affected655 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 15.1	Systematic Assessment	EG000145 affected652 at risk EG00143 affected655 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 15.1	Systematic Assessment	EG00038 affected652 at risk EG0019 affected655 at risk
Haemoglobin decreased	Investigations	MedDRA 15.1	Systematic Assessment	EG00070 affected652 at risk EG00177 affected655 at risk
Neutrophil count decreased	Investigations	MedDRA 15.1	Systematic Assessment	EG000236 affected652 at risk EG001232 affected655 at risk
White blood cell count decreased	Investigations	MedDRA 15.1	Systematic Assessment	EG000157 affected652 at risk EG001158 affected655 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG000144 affected652 at risk EG001101 affected655 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG00040 affected652 at risk EG00146 affected655 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG00026 affected652 at risk EG00144 affected655 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG00040 affected652 at risk EG00145 affected655 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG00031 affected652 at risk EG00141 affected655 at risk
Dizziness	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG00031 affected652 at risk EG00134 affected655 at risk
Dysgeusia	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG00031 affected652 at risk EG00134 affected655 at risk
Headache	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG00039 affected652 at risk EG00142 affected655 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG00040 affected652 at risk EG00147 affected655 at risk
Insomnia	Psychiatric disorders	MedDRA 15.1	Systematic Assessment	EG00031 affected652 at risk EG00138 affected655 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG00096 affected652 at risk EG001108 affected655 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG000100 affected652 at risk EG00180 affected655 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 15.1	Systematic Assessment	EG000107 affected652 at risk EG001119 affected655 at risk

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

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	Nintedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
BG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
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	Nintedanib Plus Docetaxel	Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	107	652	224	652	569	652
EG001	Placebo Plus Docetaxel	Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).	77	655	206	655	547	655