Nintedanib (BIBF 1120) in Mesothelioma | NCT01907100

NCT01907100

ID	Type	Description	Link
2012-005201-48	EudraCT Number

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo + pemetrexed/cisplatin	Placebo Comparator	Placebo controlled arm	Drug: Pemetrexed Drug: Cisplatin Drug: Placebo
Nintedanib 200mg + pemetrexed/cisplatin	Experimental	Experimental arm	Drug: Nintedanib Drug: Cisplatin Drug: Pemetrexed

Name	Type	Description	Arm Group Labels	Other Names
Nintedanib	Drug	triple kinase inhibitor; 200mg starting dose	Nintedanib 200mg + pemetrexed/cisplatin

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-Free Survival (PFS)	This outcome measure presents progression-free survival. Disease progression was defined according to the modified Response Evaluation Criteria in Solid Tumours (RECIST) criteria. Progression-free survival time was calculated as the duration from the date of randomization to the date of disease progression or death, whichever occurred first. For patients with known date of progression (or death): PFS (days) = min (date of progression, date of death) - date of randomization + 1 day. For patients without progression or death, PFS was censored at the last imaging date that showed no disease progression: PFS (days, censored) = date of last imaging showing no progression - date randomization + 1 day.	From randomization until the earliest of disease progression, death or (Phase II: cut-off date of 4-March-2016; up to 889 days) (Phase III: cut-off date of 16-March-2018; up to 31 months)

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	Overall survival was defined as the duration of time from randomization to time of death. This is the key secondary endpoint of the trial.	From randomization until the earliest of disease progression, death or (Phase II: cut-off date of 4-March-2016; up to 889 days) (Phase III: cut-off date of 16-March-2018; up to 31 months)

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35249	United States
University of California San Francisco

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
31103412	Derived	Scagliotti GV, Gaafar R, Nowak AK, Nakano T, van Meerbeeck J, Popat S, Vogelzang NJ, Grosso F, Aboelhassan R, Jakopovic M, Ceresoli GL, Taylor P, Orlandi F, Fennell DA, Novello S, Scherpereel A, Kuribayashi K, Cedres S, Sorensen JB, Pavlakis N, Reck M, Velema D, von Wangenheim U, Kim M, Barrueco J, Tsao AS. Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2019 Jul;7(7):569-580. doi: 10.1016/S2213-2600(19)30139-0. Epub 2019 May 15.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo_Phase II	Phase II part: Nintedanib matching placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 22, 2016	Sep 11, 2018

Arm/Group Information

ID	Title	Description
BG000	Placebo_Phase II	Phase II part: Nintedanib matching placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
BG001	Nintedanib_Phase II	Phase II part: Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
BG002	Placebo_Phase III	Phase III part: Nintedanib matching Placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
BG003	Nintedanib_Phase III	Phase III part: Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
BG004	Total	Total of all reporting groups

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
	ParticipantsBG00043 ParticipantsBG00144 ParticipantsBG002229 ParticipantsBG003

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00043 ParticipantsBG00144 ParticipantsBG002

Ethnicity (NIH/OMB)

Ethnicity data were not collected from any participant

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG0000 ParticipantsBG0010 ParticipantsBG002

Race (NIH/OMB)

Race was only collected where allowed by local law.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00043 ParticipantsBG00144 ParticipantsBG002

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 (PFS)

This outcome measure presents progression-free survival. Disease progression was defined according to the modified Response Evaluation Criteria in Solid Tumours (RECIST) criteria. Progression-free survival time was calculated as the duration from the date of randomization to the date of disease progression or death, whichever occurred first. For patients with known date of progression (or death): PFS (days) = min (date of progression, date of death) - date of randomization + 1 day. For patients without progression or death, PFS was censored at the last imaging date that showed no disease progression: PFS (days, censored) = date of last imaging showing no progression - date randomization + 1 day.

Randomised Set: This patient set included all randomized patients.

Posted

Median

Inter-Quartile Range

Months

From randomization until the earliest of disease progression, death or (Phase II: cut-off date of 4-March-2016; up to 889 days) (Phase III: cut-off date of 16-March-2018; up to 31 months)

ID	Title	Description
OG000	Placebo	Nintedanib matching Placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
OG001	Nintedanib	Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.

Units	Counts
Participants	OG000272 OG001273

Title

Denominators

Categories

Phase II

- ParticipantsOG00043
- ParticipantsOG00144

Title	Measurements
	OG0005.72(5.19 to 8.18)

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	Phase II Part	Proportional hazards mode		0.0174		Hazard Ratio (HR)	0.555			2-Sided	95	0.340	0.907			Hazard ratio, confidence interval and p-value obtained from proportional hazards model stratified by tumour histology (epithelioid vs. biphasic).		Other
OG000 OG001

Secondary

Overall Survival (OS)

Overall survival was defined as the duration of time from randomization to time of death.

This is the key secondary endpoint of the trial.

Randomised Set: This patient set included all randomized patients.

Posted

Median

Inter-Quartile Range

Months

From randomization until the earliest of disease progression, death or (Phase II: cut-off date of 4-March-2016; up to 889 days) (Phase III: cut-off date of 16-March-2018; up to 31 months)

ID	Title	Description
OG000	Placebo	Nintedanib matching Placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
OG001	Nintedanib	Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.

Secondary

Objective Response According to Modified RECIST- Investigator Assessment

Objective response (best overall tumour response of confirmed complete response [CR] or confirmed partial response [PR]).

Complete Response: disappearance of all target lesions Partial Response: at least a 30 % decrease in the total tumour measurement of target lesions, taking as reference the baseline total tumour measurement.

Percentage of Patients with confirmed objective response is presented. This endpoint was only evaluated for Phase III part.

Randomised Set: This patient set included all randomized patients.

Posted

Number

95% Confidence Interval

Percentage of participants

Tumour imaging was to be performed every 6 weeks until disease progression, death or start of subsequent anti-cancer therapy, whichever occurred earlier; up to 54 months

ID	Title	Description
OG000	Placebo	Nintedanib matching Placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
OG001	Nintedanib

Secondary

Disease Control According to Modified RECIST- Investigator Assessment

Disease control (best overall response of confirmed CR or PR, or Stable Disease (SD) that lasted ≥36 days) according to modified RECIST.

Percentage of Patients with Disease control is presented. This endpoint was only evaluated for Phase III part.

Randomised Set: This patient set included all randomized patients.

Posted

Number

95% Confidence Interval

Percentage of participants

Tumour imaging was to be performed every 6 weeks until disease progression, death or start of subsequent anti-cancer therapy, whichever occurred earlier; up to 54 months

ID	Title	Description
OG000	Placebo	Nintedanib matching Placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
OG001	Nintedanib	Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo_Phase II	Phase II part: Nintedanib matching placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	25	43	17	41	41	41
EG001	Nintedanib_Phase II	Phase II part: Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	22	44	16	44	44	44
EG002	Placebo_Phase III	Phase III part: Nintedanib matching Placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	63	229	89	228	219	228
EG003	Nintedanib_Phase III	Phase III part: Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	64	229	99	227	218	227

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0012 affected44 at risk EG0028 affected228 at risk EG0031 affected227 at risk
Febrile bone marrow aplasia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0023 affected228 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0023 affected228 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0022 affected228 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0013 affected44 at risk EG0027 affected228 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0024 affected228 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Deafness	Ear and labyrinth disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0012 affected44 at risk EG0022 affected228 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0013 affected44 at risk EG0027 affected228 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Large intestine perforation	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0012 affected44 at risk EG0024 affected228 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0011 affected44 at risk EG0028 affected228 at risk EG003
Asthenia	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0021 affected228 at risk EG003
Fatigue	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0023 affected228 at risk EG003
General physical health deterioration	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0010 affected44 at risk EG0022 affected228 at risk EG003
Pyrexia	General disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0013 affected44 at risk EG00210 affected228 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0010 affected44 at risk EG0022 affected228 at risk EG003
Sepsis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0010 affected44 at risk EG0022 affected228 at risk EG003
Overdose	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Blood creatinine increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0012 affected44 at risk EG0021 affected228 at risk EG003
Fibrin D dimer increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0021 affected228 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0012 affected44 at risk EG0028 affected228 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0022 affected228 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0021 affected228 at risk EG003
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0011 affected44 at risk EG0022 affected228 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0012 affected44 at risk EG0026 affected228 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0010 affected44 at risk EG0026 affected228 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0010 affected44 at risk EG0027 affected228 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0010 affected44 at risk EG0022 affected228 at risk EG003
Bone marrow toxicity	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0022 affected228 at risk EG003
Splenic infarction	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Atrioventricular block second degree	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Bundle branch block left	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Cardiac tamponade	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Cardio-respiratory arrest	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0022 affected228 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Pericarditis	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Hypoacusis	Ear and labyrinth disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Visual acuity reduced	Eye disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0022 affected228 at risk EG003
Acute abdomen	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Enteritis	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0022 affected228 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Intestinal perforation	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Pneumoperitoneum	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Chest pain	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0025 affected228 at risk EG003
Death	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Malaise	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Mucosal inflammation	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0023 affected228 at risk EG003
Pain	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0022 affected228 at risk EG003
Performance status decreased	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Bronchitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Cellulitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Device related infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Endocarditis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Escherichia bacteraemia	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Gastroenteritis norovirus	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Influenza	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Lung infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Neutropenic sepsis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Oesophageal candidiasis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Onychomycosis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Oral bacterial infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Peritonitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Pneumonia	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0024 affected228 at risk EG003
Tooth abscess	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Urosepsis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
C-reactive protein increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Ejection fraction decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Hepatic enzyme increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Platelet count decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Transaminases increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
White blood cell count decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0023 affected228 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0022 affected228 at risk EG003
Lactic acidosis	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Pleural mesothelioma malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Dizziness postural	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Encephalopathy	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Headache	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Seizure	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Spinal cord compression	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Syncope	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Depression	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Hallucination	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0025 affected228 at risk EG003
Calculus bladder	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0024 affected228 at risk EG003
Erosive balanitis	Reproductive system and breast disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Hyperventilation	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0024 affected228 at risk EG003
Stasis dermatitis	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Subcutaneous emphysema	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Aortic aneurysm	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Aortic thrombosis	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Embolism	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Hypertension	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Hypotension	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Jugular vein thrombosis	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Peripheral ischaemia	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Subclavian artery thrombosis	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Subclavian vein thrombosis	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Thrombophlebitis	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Vena cava thrombosis	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Venous thrombosis	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0021 affected228 at risk EG003
Venous thrombosis limb	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Lymphatic obstruction	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Tachyarrhythmia	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Aplasia	Congenital, familial and genetic disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Chills	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Feeling of body temperature change	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Pneumonia klebsiella	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Blood potassium decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Glomerular filtration rate decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Neuroendocrine tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Dizziness	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Nephrotic syndrome	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0011 affected44 at risk EG0020 affected228 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0010 affected44 at risk EG0020 affected228 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0009 affected41 at risk EG00116 affected44 at risk EG00294 affected228 at risk EG00376 affected227 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0005 affected41 at risk EG0012 affected44 at risk EG00228 affected228 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0009 affected41 at risk EG00122 affected44 at risk EG00282 affected228 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0017 affected44 at risk EG00218 affected228 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 20.1	Systematic Assessment	EG0009 affected41 at risk EG0014 affected44 at risk EG00224 affected228 at risk EG003
Dry eye	Eye disorders	MedDRA 20.1	Systematic Assessment	EG0003 affected41 at risk EG0010 affected44 at risk EG0024 affected228 at risk EG003
Lacrimation increased	Eye disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0017 affected44 at risk EG00218 affected228 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0003 affected41 at risk EG00111 affected44 at risk EG00210 affected228 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0003 affected41 at risk EG0019 affected44 at risk EG00211 affected228 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG00019 affected41 at risk EG00117 affected44 at risk EG00273 affected228 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG00015 affected41 at risk EG00129 affected44 at risk EG00247 affected228 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG00011 affected41 at risk EG0013 affected44 at risk EG00220 affected228 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG00034 affected41 at risk EG00137 affected44 at risk EG002134 affected228 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0005 affected41 at risk EG0013 affected44 at risk EG00216 affected228 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG00020 affected41 at risk EG00124 affected44 at risk EG00266 affected228 at risk EG003
Asthenia	General disorders	MedDRA 20.1	Systematic Assessment	EG00012 affected41 at risk EG00114 affected44 at risk EG00246 affected228 at risk EG003
Chest pain	General disorders	MedDRA 20.1	Systematic Assessment	EG0009 affected41 at risk EG0017 affected44 at risk EG00223 affected228 at risk EG003
Fatigue	General disorders	MedDRA 20.1	Systematic Assessment	EG00015 affected41 at risk EG00118 affected44 at risk EG00262 affected228 at risk EG003
Mucosal inflammation	General disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0017 affected44 at risk EG00222 affected228 at risk EG003
Oedema peripheral	General disorders	MedDRA 20.1	Systematic Assessment	EG0005 affected41 at risk EG0015 affected44 at risk EG00216 affected228 at risk EG003
Pyrexia	General disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0017 affected44 at risk EG00222 affected228 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0014 affected44 at risk EG00212 affected228 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0005 affected41 at risk EG0012 affected44 at risk EG0026 affected228 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0005 affected41 at risk EG0010 affected44 at risk EG00214 affected228 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG00117 affected44 at risk EG00210 affected228 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG00113 affected44 at risk EG0029 affected228 at risk EG003
Blood creatinine increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0016 affected44 at risk EG00226 affected228 at risk EG003
Blood magnesium decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0006 affected41 at risk EG00110 affected44 at risk EG00212 affected228 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG00110 affected44 at risk EG00213 affected228 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0003 affected41 at risk EG0018 affected44 at risk EG00226 affected228 at risk EG003
Weight decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0009 affected41 at risk EG0018 affected44 at risk EG00223 affected228 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG00016 affected41 at risk EG00117 affected44 at risk EG00266 affected228 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0014 affected44 at risk EG00213 affected228 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0008 affected41 at risk EG00113 affected44 at risk EG00220 affected228 at risk EG003
Dizziness	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0005 affected41 at risk EG0013 affected44 at risk EG00218 affected228 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG00011 affected41 at risk EG00111 affected44 at risk EG00227 affected228 at risk EG003
Headache	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0015 affected44 at risk EG00223 affected228 at risk EG003
Lethargy	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG00013 affected41 at risk EG0016 affected44 at risk EG0025 affected228 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0006 affected41 at risk EG0019 affected44 at risk EG00218 affected228 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0014 affected44 at risk EG00219 affected228 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0018 affected44 at risk EG00212 affected228 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0006 affected41 at risk EG00115 affected44 at risk EG00233 affected228 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0007 affected41 at risk EG0017 affected44 at risk EG00226 affected228 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0003 affected41 at risk EG0011 affected44 at risk EG00220 affected228 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0005 affected41 at risk EG0016 affected44 at risk EG0028 affected228 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0007 affected41 at risk EG00111 affected44 at risk EG00223 affected228 at risk EG003
Hypertension	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0006 affected41 at risk EG0016 affected44 at risk EG00221 affected228 at risk EG003
White blood cell count decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0012 affected44 at risk EG00215 affected228 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0012 affected44 at risk EG00215 affected228 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0011 affected44 at risk EG00214 affected228 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0011 affected44 at risk EG00213 affected228 at risk EG003
Hypoacusis	Ear and labyrinth disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0014 affected44 at risk EG0024 affected228 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0012 affected44 at risk EG0022 affected228 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0013 affected44 at risk EG00211 affected228 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0013 affected44 at risk EG0022 affected228 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0014 affected44 at risk EG00211 affected228 at risk EG003
Influenza	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0013 affected44 at risk EG0024 affected228 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0019 affected44 at risk EG0026 affected228 at risk EG003
Blood glucose increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0015 affected44 at risk EG0021 affected228 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0013 affected44 at risk EG0021 affected228 at risk EG003
Blood potassium decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0014 affected44 at risk EG0020 affected228 at risk EG003
Blood urea increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0003 affected41 at risk EG0018 affected44 at risk EG00210 affected228 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0014 affected44 at risk EG0022 affected228 at risk EG003
Platelet count decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0018 affected44 at risk EG0027 affected228 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0003 affected41 at risk EG0014 affected44 at risk EG0028 affected228 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0003 affected41 at risk EG0010 affected44 at risk EG0027 affected228 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected41 at risk EG0013 affected44 at risk EG0025 affected228 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0014 affected44 at risk EG0029 affected228 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0012 affected44 at risk EG00210 affected228 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected41 at risk EG0012 affected44 at risk EG00211 affected228 at risk EG003
Neurotoxicity	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0003 affected41 at risk EG0011 affected44 at risk EG0024 affected228 at risk EG003
Depression	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0003 affected41 at risk EG0011 affected44 at risk EG0022 affected228 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected41 at risk EG0013 affected44 at risk EG0022 affected228 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0006 affected41 at risk EG0012 affected44 at risk EG0024 affected228 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0003 affected41 at risk EG0010 affected44 at risk EG0027 affected228 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected41 at risk EG0013 affected44 at risk EG00210 affected228 at risk EG003

Certain Agreements

Ancestor Terms

ID	Term
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D005971	Glutamates
D024342	Amino Acids, Acidic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D000600	Amino Acids, Dicarboxylic
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds

Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.

ID	Term
D000236	Adenoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D018301	Neoplasms, Mesothelial