Effect of Roflumilast in Chronic Obstructive Pulmonary Di... | NCT00424268

ID	Type	Description	Link
2006-004508-37	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
Roflumilast	Active Comparator	Roflumilast 500 µg underlying medication: tiotropium 18 µg, once daily, inhaled	Drug: Roflumilast
Placebo	Placebo Comparator	Placebo underlying medication: tiotropium 18 µg, once daily, inhaled	Drug: Placebo

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

Outcomes Module

Primary Outcomes

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 24 weeks of treatment

Secondary Outcomes

Measure	Description	Time Frame
Post-bronchodilator FEV1	Mean change from baseline during the treatment period in post-bronchodilator FEV1 [L]	Change from baseline over 24 weeks of treatment
COPD Exacerbation Rate (Moderate or Severe)

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
AstraZeneca AstraZeneca	AstraZeneca	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Altana Pharma/Nycomed Investigational Site		Feldbach		8330	Austria
Altana Pharma/Nycomed Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
19716961	Result	Fabbri LM, Calverley PM, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ, Rabe KF; M2-127 and M2-128 study groups. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet. 2009 Aug 29;374(9691):695-703. doi: 10.1016/S0140-6736(09)61252-6.
20102307

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Roflumilast	Roflumilast 500 µg, once daily, oral and tiotropium 18 µg, once daily, inhaled
FG001	Placebo	Placebo, once daily, oral and tiotropium 18 µg, once daily, inhaled

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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].

Arm/Group Information

ID	Title	Description
BG000	Roflumilast	Roflumilast 500 µg, once daily, oral and tiotropium 18 µg, once daily, inhaled
BG001	Placebo	Placebo, once daily, oral and tiotropium 18 µg, once daily, inhaled
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
	OG00065± 12 OG001-16± 12

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 24 weeks of treatment taking all post-randomization measurements into account).	<0.0001	No adjustment of the significance level (0.05) was done as a hierarchical approach for hypotheses testing was used.	Mean Difference (Net)	80	Standard Error of the Mean	15	2-Sided	95	51	110				No	Superiority or Other

Secondary

Post-bronchodilator FEV1

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 24 weeks of treatment

ID	Title	Description
OG000	Roflumilast	Roflumilast 500 µg, once daily, oral and tiotropium 18 µg, once daily, inhaled
OG001	Placebo	Placebo, once daily, oral and tiotropium 18 µg, once daily, inhaled

Units	Counts
Participants	OG000

Secondary

COPD Exacerbation Rate (Moderate or Severe)

ITT analysis

Posted

Mean

95% Confidence Interval

exacerbations per patient per year

24 weeks treatment period

ID	Title	Description
OG000	Roflumilast	Roflumilast 500 µg, once daily, oral and tiotropium 18 µg, once daily, inhaled
OG001	Placebo	Placebo, once daily, oral and tiotropium 18 µg, once daily, inhaled

Units	Counts
Participants	OG000

Secondary

Transition Dyspnea Index (TDI) Focal Score

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 24 weeks of treatment

ID	Title	Description
OG000	Roflumilast	Roflumilast 500 µg, once daily, oral and tiotropium 18 µg, once daily, inhaled
OG001	Placebo	Placebo, once daily, oral and tiotropium 18 µg, once daily, inhaled

Units	Counts
Participants

Secondary

Shortness of Breath Questionnaire (SOBQ) Total Score

Mean change from baseline during the treatment period in SOBQ. This is a 24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living. The questions were administered at visits V0, V2, V3, V4, V5, V6 and Vend to assess the perceived shortness of breath of the patient. For each activity listed in the questionnaire the patient should rate his/her breathlessness on a scale between zero and five, where zero is "not at all breathless" and five is "maximally breathless or too breathless to do the activity".

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 24 weeks of treatment

ID	Title	Description
OG000	Roflumilast	Roflumilast 500 µg, once daily, oral and tiotropium 18 µg, once daily, inhaled
OG001	Placebo	Placebo, once daily, oral and tiotropium 18 µg, once daily, inhaled

Units	Counts
Participants

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	Roflumilast	Roflumilast 500 µg, once daily, oral and tiotropium 18 µg, once daily, inhaled			22	374	106	374
EG001	Placebo	Placebo, once daily, oral and tiotropium 18 µg, once daily, inhaled			21	369	76	369

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	EG0004 events4 affected374 at risk EG0015 events5 affected369 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Haematochezia	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0002 events2 affected374 at risk EG0010 events0 affected369 at risk
Colitis	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Colonic polyp	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Angina pectoris	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Cardiac failure	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Myocardial infarction	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Metastatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Pancreatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0011 events1 affected369 at risk
Lymphoid tissue hyperplasia	Blood and lymphatic system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Appendicitis	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Perianal abscess	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Pneumonia	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Post procedural myocardial infarction	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Guillain-Barre syndrome	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Retinal artery embolism	Eye disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Chest pain	General disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Weight decreased	Investigations	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Metatarsalgia	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Confusional state	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Renal failure chronic	Renal and urinary disorders	MedDRA (11.0)	Systematic Assessment	EG0000 events0 affected374 at risk EG0011 events1 affected369 at risk
Vascular operation	Surgical and medical procedures	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk
Aortic aneurysm	Vascular disorders	MedDRA (11.0)	Systematic Assessment	EG0001 events1 affected374 at risk EG0010 events0 affected369 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	non-serious	EG00064 events54 affected374 at risk EG00180 events63 affected369 at risk
Nasopharyngitis	Infections and infestations	MedDRA (11.0)	Systematic Assessment		EG00024 events21 affected374 at risk EG00123 events20 affected369 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment		EG00038 events33 affected374 at risk EG0012 events2 affected369 at risk
Weight decreased	Investigations	MedDRA (11.0)	Systematic Assessment	non-serious	EG00020 events20 affected374 at risk EG0012 events2 affected369 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