Study to Assess the Efficacy and Safety of Simtuzumab (GS... | NCT01769196

ID	Type	Description	Link
2012-001571-36	EudraCT Number

Status Module

Oversight 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
Simtuzumab	Experimental	Participants will receive simtuzumab for up to 254 weeks.	Drug: Simtuzumab
Simtuzumab Placebo	Placebo Comparator	Participants will receive simtuzumab placebo for up to 254 weeks.	Drug: Simtuzumab placebo

Name	Type	Description	Arm Group Labels	Other Names
Simtuzumab	Drug	125 mg/mL single-dose vials administered subcutaneously once a week	Simtuzumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression Free Survival	Progression free survival (PFS) was defined as the categorical decrease in forced vital capacity (FVC) % predicted (≥ 10% relative decrease in FVC and ≥ 5% absolute decrease in FVC from baseline) with confirmation at a consecutive visit at least 2 weeks later using the same criteria.	Up to 148 weeks
PFS Among the Participants With sLOXL2 ≥ 50th Percentile		Up to 148 weeks
PFS Among the Participants With sLOXL2 ≥ 75th Percentile		Up to 148 weeks

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	Overall survival was defined as the time from randomization date to death that occurred prior to the last dose date plus 30 days.	Up to 151 weeks
Overall Survival Among the Participants With sLOXL2 ≥ 50th Percentile

Eligibility Module

Name	Affiliation	Role
Gilead Study Director	Gilead Sciences	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35294	United States
Arizona Pulmonary Specialists, Ltd.

References Module

Citations

PubMed Identifier	Type	Citation
27939076	Background	Raghu G, Brown KK, Collard HR, Cottin V, Gibson KF, Kaner RJ, Lederer DJ, Martinez FJ, Noble PW, Song JW, Wells AU, Whelan TP, Wuyts W, Moreau E, Patterson SD, Smith V, Bayly S, Chien JW, Gong Q, Zhang JJ, O'Riordan TG. Efficacy of simtuzumab versus placebo in patients with idiopathic pulmonary fibrosis: a randomised, double-blind, controlled, phase 2 trial. Lancet Respir Med. 2017 Jan;5(1):22-32. doi: 10.1016/S2213-2600(16)30421-0. Epub 2016 Dec 7.
	Result	Humphries SM, O'Riordan TG, Zhang JJ, Bayly S, Sood R, Hayden A, Lynch DA; Relationship Baseline Fibrosis Score to Lung Function in A Clinical Trial Population with Idiopathic Pulmonary Fibrosis. ATS International Conference, 2016 May 13-18, San Francisco CA.
	Result	Raghu G, Brown K, Collard H, Lederer D, Martinez F, Noble P, Song JW, Wells A, Whelan T, Moreau E, Patterson S, Bayly S, Chien J, Zhang J, O'Riordan T; Simtuzumab in Idiopathic Pulmonary Fibrosis: Results of a Randomized Clinical Trial. ERS Congress, 2016 September 3-7, London, UK.

Results Section

Participant Flow Module

ID	Title	Description
FG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
FG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
BG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week
BG002	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

Title	Measurements
	BG00067.7± 7.60 BG00168.5± 7.07 BG00268.1± 7.34

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00045 BG00147 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Asian

Title	Measurements
	BG00035 BG00136 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Hispanic or Latino

Title	Measurements
	BG0005 BG0017 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG000102 BG001106 BG002

Forced vital capacity (FVC) Percent Predicted

Mean

Standard Deviation

FVC % predicted

Title

Denominators

Categories

Title	Measurements
	BG00061.4± 12.17 BG00162.3± 12.22 BG002

FVC % Predicted Category

Count of Participants

Participants

Title

Denominators

Categories

Mild

Title	Measurements
	BG00037 BG00146 BG002

Baseline Serum LOXL2

Mean

Standard Deviation

pg/mL

Title

Denominators

Categories

Title	Measurements
	BG00089.8± 70.06 BG00186.7± 51.99 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression Free Survival

Progression free survival (PFS) was defined as the categorical decrease in forced vital capacity (FVC) % predicted (≥ 10% relative decrease in FVC and ≥ 5% absolute decrease in FVC from baseline) with confirmation at a consecutive visit at least 2 weeks later using the same criteria.

ITT Analysis Set

Posted

Median

95% Confidence Interval

months

Up to 148 weeks

ID	Title	Description
OG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
OG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week

Units	Counts
Participants	OG000272 OG001272

Title

Denominators

Categories

Title	Measurements
	OG00012.6(11.3 to 14.4) OG00115.4(12.6 to 19.1)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.329		Hazard Ratio (HR)	1.13			2-Sided	95	0.88	1.45			Hazard ratio was estimated from Cox regression model adjusted for treatment and stratified for screening post-bronchodilator FVC % predicted, sLOXL2 level categories, and concomitant pirfenidone/nintedanib use at time of screening.		Superiority	The null hypothesis was that there is no difference in PFS between simtuzumab and simtuzumab placebo. The alternative hypothesis was that there is a difference. These hypotheses were evaluated using stratified log-rank test, adjusted for screening post-bronchodilator FVC % predicted, sLOXL2 level categories and concomitant use of pirfenidone or nintedanib (P/N) at time of screening.

Primary

PFS Among the Participants With sLOXL2 ≥ 50th Percentile

Participants in the ITT Analysis Set with serum LOXL2 (sLOXL2) ≥ 50th percentile in peripheral blood were analyzed.

Posted

Median

95% Confidence Interval

months

Up to 148 weeks

ID	Title	Description
OG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
OG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week

Units	Counts
Participants	OG000

Primary

PFS Among the Participants With sLOXL2 ≥ 75th Percentile

Participants in the ITT Analysis Set with sLOXL2 ≥ 75th percentile in peripheral blood were analyzed.

Posted

Median

95% Confidence Interval

months

Up to 148 weeks

ID	Title	Description
OG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
OG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week

Units	Counts
Participants	OG000

Secondary

Overall Survival (OS)

Overall survival was defined as the time from randomization date to death that occurred prior to the last dose date plus 30 days.

ITT Analysis Set

Posted

Median

95% Confidence Interval

months

Up to 151 weeks

ID	Title	Description
OG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
OG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week

Units	Counts
Participants	OG000

Secondary

Overall Survival Among the Participants With sLOXL2 ≥ 50th Percentile

Participants in the ITT Analysis Set with sLOXL2 ≥ 50th percentile in peripheral blood were analyzed.

Posted

Median

95% Confidence Interval

months

Up to 151 weeks

ID	Title	Description
OG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
OG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week

Units	Counts
Participants	OG000

Secondary

Overall Survival Among the Participants With sLOXL2 ≥ 75th Percentile

Participants in the ITT Analysis Set with sLOXL2 ≥ 75th percentile in peripheral blood were analyzed.

Posted

Median

95% Confidence Interval

months

Up to 151 weeks

ID	Title	Description
OG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
OG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week

Units	Counts
Participants	OG000

Secondary

Relative Change From Baseline in FVC % Predicted

FVC was defined as the volume of air (liters) that can forcibly be blown out after taking a full breath. FVC % predicted was defined as FVC % of the participant divided by the average FVC % in the population for any person of similar age, sex, and body composition.
Adjusted means were from mixed model repeated measures (MMRM) model with baseline FVC % predicted, sLOXL2 level, concomitant pirfenidone/nintedanib use (never vs. ever), treatment, visit, and treatment-by-visit interaction terms, including all data up to Week 130
The relative change was calculated as 100% * ( value at later time point minus value at baseline ) / value at baseline, with lower values indicating a decrease and higher values indicating an increase.

Participants in the ITT Analysis Set with available data were analyzed. Any participant with available outcome data on baseline or post-baseline was included in the MMRM model, thus all 272 participants in each of the two treatment groups were included in this analysis.

Posted

Least Squares Mean

Standard Error

Percent change in FVC % predicted

Weeks 54, 106, and 130

ID	Title	Description
OG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
OG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week

Secondary

Definite Acute Exacerbations of IPF Among Adjudicated Respiratory Hospitalizations

Participants in the ITT Analysis Set with adjudicated respiratory hospitalizations were analyzed.

Posted

Count of Participants

Participants

Up to 148 weeks

ID	Title	Description
OG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
OG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week

Units	Counts
Participants	OG000

Secondary

Number of Adjudicated Respiratory Hospitalizations (ARP) Among Total Hospitalizations

Participants in ITT Analysis Set with total hospitalizations were analyzed.

Posted

Count of Participants

Participants

Up to 148 weeks

ID	Title	Description
OG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
OG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week

Units	Counts
Participants	OG000

Secondary

Number of Participants Experiencing Adjudicated Respiratory Deaths Among Those With Adjudicated Death

Participants in the ITT Analysis Set with adjudicated deaths were analyzed.

Posted

Count of Participants

Participants

Up to 148 weeks

ID	Title	Description
OG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
OG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week

Units	Counts
Participants	OG000

Secondary

Absolute Change From Baseline in 6 Minute Walk Distance (6MWD)

Adjusted means were from MMRM model with baseline 6MWD, FVC % predicted, sLOXL2 level, concomitant pirfenidone/nintedanib use (never vs. ever), treatment, visit, and treatment-by-visit interaction terms, including all data up to Week 130.
The absolute change was calculated as value at later time point minus value at baseline, with lower values indicating a decrease and higher values indicating an increase.

Posted

Least Squares Mean

Standard Error

Meters

Weeks 58, 106, and 130

ID	Title	Description
OG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
OG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week

Units	Counts
Participants

Secondary

Absolute Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Score

The SGRQ is a disease-specific questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Patients respond to questions about symptoms (frequency & severity) and impact components (social functioning and psychological disturbances resulting from airways disease). Scores range from 0 to 100, with higher scores indicating more limitations.
The absolute change was calculated as value at later time point minus value at baseline, with lower values indicating a decrease and higher values indicating an increase.

Posted

Least Squares Mean

Standard Error

units on a scale

Week 58, 106, and 130

ID	Title	Description
OG000	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week
OG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week

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	Simtuzumab	Simtuzumab 125 mg/mL administered subcutaneously once a week	31	271	101	271	237	271
EG001	Simtuzumab Placebo	Simtuzumab placebo administered subcutaneously once a week	32	272	97	272	246	272

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected271 at risk EG0015 affected272 at risk
Acute right ventricular failure	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Angina pectoris	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0010 affected272 at risk
Aortic valve stenosis	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected271 at risk EG0011 affected272 at risk
Atrial flutter	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0010 affected272 at risk
Cardiac arrest	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Cardiac failure	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0012 affected272 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Cardiomyopathy	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Coronary artery disease	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0013 affected272 at risk
Coronary artery occlusion	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0011 affected272 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Pleuropericarditis	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Right ventricular dysfunction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Right ventricular failure	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0010 affected272 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Diverticulum intestinal haemorrhagic	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Gastritis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Melaena	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Mesenteric venous occlusion	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0012 affected272 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Asthenia	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0012 affected272 at risk
Chest discomfort	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0013 affected272 at risk
Death	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0010 affected272 at risk
General physical health deterioration	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0010 affected272 at risk
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0010 affected272 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0012 affected272 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected271 at risk EG0011 affected272 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0010 affected272 at risk
Hepatic mass	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Hepatic necrosis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Appendicitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Bacteraemia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0010 affected272 at risk
Bronchitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0010 affected272 at risk
Cellulitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Endocarditis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Furuncle	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Gastroenteritis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0011 affected272 at risk
Hepatitis E	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Influenza	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Intervertebral discitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0014 affected272 at risk
Lung infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Mycetoma mycotic	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Oropharyngitis fungal	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Osteomyelitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Pneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00016 affected271 at risk EG00118 affected272 at risk
Pneumonia klebsiella	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Pyelonephritis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Respiratory moniliasis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Respiratory syncytial virus infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0013 affected272 at risk
Sepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0011 affected272 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0011 affected272 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 affected271 at risk EG0010 affected272 at risk
Urosepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Post procedural stroke	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Blood creatinine increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Blood urea increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Ejection fraction decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
International normalised ratio increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0011 affected272 at risk
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Spondylolysis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Bronchioloalveolar carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Gastrointestinal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0011 affected272 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Metastases to lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Oesophageal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Squamous cell carcinoma of lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0011 affected272 at risk
Squamous cell carcinoma of the tongue	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Amnesia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Chronic inflammatory demyelinating polyradiculoneuropathy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Facial paresis	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Polyneuropathy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Presyncope	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Seizure	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Syncope	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0012 affected272 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0012 affected272 at risk
VIth nerve paralysis	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Calculus urinary	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Glomerulonephritis	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Goodpasture's syndrome	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Haematuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected271 at risk EG0011 affected272 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0011 affected272 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00010 affected271 at risk EG0017 affected272 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected271 at risk EG0012 affected272 at risk
Idiopathic pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00031 affected271 at risk EG00135 affected272 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Nasal polyps	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0013 affected272 at risk
Pulmonary alveolar haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0013 affected272 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected271 at risk EG0010 affected272 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0011 affected272 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected271 at risk EG0014 affected272 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Aortic stenosis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected271 at risk EG0011 affected272 at risk
Circulatory collapse	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0011 affected272 at risk
Femoral artery occlusion	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Hypertension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Peripheral vascular disorder	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected271 at risk EG0011 affected272 at risk
Vasculitis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected271 at risk EG0010 affected272 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00016 affected271 at risk EG00113 affected272 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00044 affected271 at risk EG00147 affected272 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00021 affected271 at risk EG00122 affected272 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00033 affected271 at risk EG00135 affected272 at risk
Asthenia	General disorders	MedDRA 18.0	Systematic Assessment	EG00015 affected271 at risk EG00117 affected272 at risk
Chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG00018 affected271 at risk EG00116 affected272 at risk
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG00049 affected271 at risk EG00148 affected272 at risk
Injection site bruising	General disorders	MedDRA 18.0	Systematic Assessment	EG00017 affected271 at risk EG00110 affected272 at risk
Oedema peripheral	General disorders	MedDRA 18.0	Systematic Assessment	EG00021 affected271 at risk EG00112 affected272 at risk
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG00021 affected271 at risk EG00112 affected272 at risk
Bronchitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00032 affected271 at risk EG00139 affected272 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0008 affected271 at risk EG00115 affected272 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00036 affected271 at risk EG00143 affected272 at risk
Respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00014 affected271 at risk EG00117 affected272 at risk
Sinusitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00016 affected271 at risk EG00114 affected272 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00057 affected271 at risk EG00157 affected272 at risk
Weight decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG00025 affected271 at risk EG00124 affected272 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG00029 affected271 at risk EG00134 affected272 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00035 affected271 at risk EG00122 affected272 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00027 affected271 at risk EG00128 affected272 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected271 at risk EG00114 affected272 at risk
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG00031 affected271 at risk EG00126 affected272 at risk
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG00032 affected271 at risk EG00135 affected272 at risk
Depression	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG00014 affected271 at risk EG00112 affected272 at risk
Insomnia	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG00015 affected271 at risk EG00117 affected272 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG000102 affected271 at risk EG00193 affected272 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00098 affected271 at risk EG00173 affected272 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00030 affected271 at risk EG00129 affected272 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00016 affected271 at risk EG0019 affected272 at risk
Idiopathic pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00033 affected271 at risk EG00127 affected272 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00016 affected271 at risk EG00115 affected272 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00022 affected271 at risk EG00118 affected272 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00019 affected271 at risk EG00115 affected272 at risk
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00014 affected271 at risk EG0014 affected272 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG00017 affected271 at risk EG0018 affected272 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG00022 affected271 at risk EG00121 affected272 at risk
Hypertension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG00015 affected271 at risk EG00112 affected272 at risk

ID	Term
D011658	Pulmonary Fibrosis
D017563	Lung Diseases, Interstitial
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms