Effect of Roflumilast on Exacerbation Rate in Patients Wi... | NCT00297115

Label	Type	Description	Intervention Names
Roflumilast	Active Comparator	500 mcg, once daily, oral administration in the morning	Drug: Roflumilast
Placebo	Placebo Comparator	once daily	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Roflumilast	Drug	500 mcg, once daily, oral administration in the morning	Roflumilast

Measure	Description	Time Frame
Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1)	Mean change from baseline during the treatment period in pre-bronchodilator FEV1 [L]	Change from baseline over 52 weeks of treatment
COPD Exacerbation Rate (Moderate or Severe)	Mean rate of COPD exacerbations requiring oral or parenteral glucocorticosteroids (=moderate COPD exacerbations), or requiring hospitalization, or leading to death (=severe COPD exacerbations), per patient per year. A COPD exacerbation is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough and/or sputum beyond day-to-day variability sufficient to warrant a change in management [American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005].	52 weeks treatment period

Measure	Description	Time Frame
Post-bronchodilator FEV1 [L]	Mean change from baseline during the treatment period in post-bronchodilator FEV1 [L]	Change from baseline over 52 weeks of treatment
Time to Mortality Due to Any Reason

Name	Affiliation	Role
AstraZeneca AstraZeneca	AstraZeneca	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Altana Pharma/Nycomed Investigational Site		Bayou La Batre	Alabama	36509	United States
Altana Pharma/Nycomed Investigational Site

PubMed Identifier	Type	Citation	Retractions
19716960	Result	Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ; M2-124 and M2-125 study groups. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet. 2009 Aug 29;374(9691):685-94. doi: 10.1016/S0140-6736(09)61255-1.
28419462	Derived	Facius A, Krause A, Claret L, Bruno R, Lahu G. Modeling and Simulation of Pivotal Clinical Trials Using Linked Models for Multiple Endpoints in Chronic Obstructive Pulmonary Disease With Roflumilast. J Clin Pharmacol. 2017 Aug;57(8):1042-1052. doi: 10.1002/jcph.885. Epub 2017 Apr 17.

ID	Title	Description
FG000	Roflumilast	500 mcg, once daily, oral administration in the morning
FG001	Placebo	once daily

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

Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1)

Mean change from baseline during the treatment period in pre-bronchodilator FEV1 [L]

ITT (Intention to Treat) analysis. Number of participants analyzed = number of participants with data available.

Posted

Least Squares Mean

Standard Error

Change from baseline over 52 weeks of treatment

ID	Title	Description
OG000	Roflumilast	500 mcg, once daily, oral administration in the morning
OG001	Placebo	once daily

Units	Counts
Participants	OG000730 OG001766

Title

Denominators

Categories

Title	Measurements
	OG00033± 7 OG001-25± 7

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		ANCOVA	Repeated measurements analysis (change from baseline over 52 weeks of treatment taking all post-randomization measurements into account).	<0.0001	No adjustment of the significance level was done as a hierarchical approach for hypotheses testing was used.	Mean Difference (Net)	58	Standard Error of the Mean	9	2-Sided	95	41	75				No	Superiority or Other

Primary

COPD Exacerbation Rate (Moderate or Severe)

Mean rate of COPD exacerbations requiring oral or parenteral glucocorticosteroids (=moderate COPD exacerbations), or requiring hospitalization, or leading to death (=severe COPD exacerbations), per patient per year. A COPD exacerbation is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough and/or sputum beyond day-to-day variability sufficient to warrant a change in management [American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005].

ITT analysis.

Posted

Mean

95% Confidence Interval

exacerbations per patient per year

52 weeks treatment period

ID	Title	Description
OG000	Roflumilast	500 mcg, once daily, oral administration in the morning
OG001	Placebo	once daily

Units	Counts
Participants	OG000

Secondary

Post-bronchodilator FEV1 [L]

Mean change from baseline during the treatment period in post-bronchodilator FEV1 [L]

ITT analysis. Number of participants analyzed = number of participants with data available.

Posted

Least Squares Mean

Standard Error

Change from baseline over 52 weeks of treatment

ID	Title	Description
OG000	Roflumilast	500 mcg, once daily, oral administration in the morning
OG001	Placebo	once daily

Units	Counts
Participants	OG000

Secondary

Time to Mortality Due to Any Reason

ITT analysis. Number of participants analyzed = number of participants who died.

Posted

Mean

Standard Deviation

days

52 weeks treatment period

ID	Title	Description
OG000	Roflumilast	500 mcg, once daily, oral administration in the morning
OG001	Placebo	once daily

Units	Counts
Participants	OG00025

Secondary

Natural Log-transformed C-reactive Protein (CRP)

Mean change from baseline to the last post randomization measurement in natural log-transformed CRP

ITT analysis. Number of participants analyzed = number of participants with data available.

Posted

Least Squares Mean

95% Confidence Interval

mg/L

Change from baseline to last post randomization measurement (52 weeks)

ID	Title	Description
OG000	Roflumilast	500 mcg, once daily, oral administration in the morning
OG001	Placebo	once daily

Units	Counts
Participants	OG000

Secondary

Mean Transition Dyspnea Index (TDI) Focal Score During the Treatment Period

The TDI is a recognized questionnaire to measure dyspnea in an out patient COPD population. At baseline, 3 components of dyspnea, each graded with 4 questions, were asked: - Functional Impairment - Magnitude of Task - Magnitude of Effort At each of the post-randomization visits questions from the TDI were asked related to 3 components: Change in - Functional Impairment - Magnitude of Task - Magnitude of Effort Each question in the TDI is graded from -3 (major deterioration) to +3 (major improvement). This results in a TDI Focal Score ranging from -9 to +9.

ITT analysis. Number of participants analyzed = number of participants with data available.

Posted

Least Squares Mean

Standard Error

scores on a scale

Change from baseline over 52 weeks of treatment

ID	Title	Description
OG000	Roflumilast	500 mcg, once daily, oral administration in the morning
OG001	Placebo	once daily

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG000110 events87 affected778 at risk EG001160 events121 affected790 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0004 events4 affected778 at risk EG0016 events5 affected790 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0014 events4 affected790 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0011 events1 affected790 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0012 events2 affected790 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0012 events2 affected790 at risk
Respiratory arrest	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0011 events1 affected790 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Hyperventilation	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events1 affected778 at risk EG0010 events0 affected790 at risk
Hypoventilation	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Respiratory acidosis	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Pneumonia	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG00018 events18 affected778 at risk EG00110 events10 affected790 at risk
Bronchopneumonia	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0013 events3 affected790 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0013 events3 affected790 at risk
Bronchitis	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0010 events0 affected790 at risk
Lobar pneumonia	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0012 events2 affected790 at risk
Viral infection	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0011 events1 affected790 at risk
Appendicitis	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Cellulitis	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Localised infection	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Pneumonia primary atypical	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Septic shock	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Urinary tract infection	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Urosepsis	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Myocardial infarction	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0014 events4 affected790 at risk
Angina pectoris	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0013 events3 affected790 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0003 events3 affected778 at risk EG0012 events2 affected790 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0013 events3 affected790 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0012 events2 affected790 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0003 events3 affected778 at risk EG0010 events0 affected790 at risk
Coronary artery disease	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0013 events3 affected790 at risk
Right ventricular failure	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0012 events2 affected790 at risk
Bradycardia	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0012 events2 affected790 at risk
Cardiac arrest	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0010 events0 affected790 at risk
Cardiac failure	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0013 events1 affected790 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0010 events0 affected790 at risk
Cor pulmonale	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0011 events1 affected790 at risk
Left ventricular failure	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0011 events1 affected790 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0011 events1 affected790 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0012 events2 affected790 at risk
Angina unstable	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Atrioventricular block	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Mitral valve stenosis	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Supraventricular tachyarrhythmia	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Tachycardia	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0004 events4 affected778 at risk EG0011 events1 affected790 at risk
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0011 events1 affected790 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0011 events1 affected790 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0012 events2 affected790 at risk
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0012 events2 affected790 at risk
Plasmacytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0012 events2 affected790 at risk
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0012 events2 affected790 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Adenoma benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Bronchial carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Carcinoid tumour of the small bowel	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Chronic lymphocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Gastric cancer stage II	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Metastasis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Metastatic carcinoma of the bladder	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Neuroendocrine carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Non-small cell lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Oesophageal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Small cell lung cancer stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0004 events4 affected778 at risk EG0010 events0 affected790 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0011 events1 affected790 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0010 events0 affected790 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0012 events2 affected790 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0011 events1 affected790 at risk
Intestinal polyp	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0010 events0 affected790 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0012 events2 affected790 at risk
Colitis	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Nausea	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Pancreatic cyst	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Vomiting	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Sudden death	General disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0013 events3 affected790 at risk
Chest pain	General disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0013 events3 affected790 at risk
Non-cardiac chest pain	General disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0012 events2 affected790 at risk
Death	General disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0012 events2 affected790 at risk
Asthenia	General disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Malaise	General disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Metaplasia	General disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Pyrexia	General disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Ulcer haemorrhage	General disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0013 events3 affected790 at risk
Cerebral infarction	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0010 events0 affected790 at risk
Syncope	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0011 events1 affected790 at risk
Anoxic encephalopathy	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Dizziness	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Encephalopathy	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Hypoxic encephalopathy	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Optic neuritis	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Wernicke's encephalopathy	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Comminuted fracture	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Device dislocation	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Eye penetration	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Fibula fracture	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Foreign body trauma	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Arterial stenosis	Vascular disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Femoral artery occlusion	Vascular disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Haematoma	Vascular disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Hypertension	Vascular disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Hypotension	Vascular disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Ischaemia	Vascular disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Peripheral artery aneurysm	Vascular disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0012 events2 affected790 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Polycythaemia	Blood and lymphatic system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (11.0)	Systematic Assessment	EG0003 events3 affected778 at risk EG0010 events0 affected790 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events1 affected778 at risk EG0010 events0 affected790 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (11.0)	Systematic Assessment	EG0003 events3 affected778 at risk EG0011 events1 affected790 at risk
Micturition disorder	Renal and urinary disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Renal failure	Renal and urinary disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Depression	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0011 events1 affected790 at risk
Alcohol withdrawal syndrome	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Completed suicide	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Mental status changes	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Suicidal ideation	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Leukocytoclastic vasculitis	Skin and subcutaneous tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0011 events1 affected790 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Coronary artery bypass	Surgical and medical procedures	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Endarterectomy	Surgical and medical procedures	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Knee arthroplasty	Surgical and medical procedures	MedDRA (11.0)	Systematic Assessment	EG0002 events1 affected778 at risk EG0010 events0 affected790 at risk
Cataract	Eye disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0011 events1 affected790 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk
Blood creatinine increased	Investigations	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Blood urea increased	Investigations	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected778 at risk EG0010 events0 affected790 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected778 at risk EG0010 events0 affected790 at risk
Anti-neutrophil cytoplasmic antibody positive vasculitis	Immune system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected778 at risk EG0011 events1 affected790 at risk

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	Roflumilast	500 mcg, once daily, oral administration in the morning
BG001	Placebo	once daily
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Roflumilast	500 mcg, once daily, oral administration in the morning			157	778	145	778
EG001	Placebo	once daily			183	790	81	790