ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect of Roflumilast on Lung Function in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Salmeterol: The EOS Study (BY217/M2-127) (EOS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00313209
Recruitment Status : Completed
First Posted : April 12, 2006
Results First Posted : May 19, 2011
Last Update Posted : December 14, 2016
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease (COPD)
Interventions Drug: Roflumilast
Drug: Placebo
Enrollment 933

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Roflumilast Placebo
Hide Arm/Group Description Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Period Title: Overall Study
Started 466 [1] 467 [1]
Completed 359 385
Not Completed 107 82
[1]
Includes all randomized patients who took at least one dose of the investigational drug.
Arm/Group Title Roflumilast Placebo Total
Hide Arm/Group Description Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled Total of all reporting groups
Overall Number of Baseline Participants 466 467 933
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 466 participants 467 participants 933 participants
64.9  (8.7) 64.9  (9.3) 64.9  (9.0)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 466 participants 467 participants 933 participants
Female
147
  31.5%
168
  36.0%
315
  33.8%
Male
319
  68.5%
299
  64.0%
618
  66.2%
1.Primary Outcome
Title Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1)
Hide Description Mean change from baseline during the treatment period in pre-bronchodilator FEV1 [L]
Time Frame Change from baseline over 24 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT (Intention to Treat) analysis. Number of participants analyzed = number of participants with data available.
Arm/Group Title Roflumilast Placebo
Hide Arm/Group Description:
Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Overall Number of Participants Analyzed 456 463
Least Squares Mean (Standard Error)
Unit of Measure: mL
39  (9) -10  (9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roflumilast, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No adjustment of the significance level (0.05) was done as a hierarchical approach for hypotheses testing was used.
Method ANCOVA
Comments Repeated measurements analysis (change from baseline over 24 weeks of treatment taking all post-randomization measurements into account).
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 49
Confidence Interval (2-Sided) 95%
27 to 71
Parameter Dispersion
Type: Standard Error of the mean
Value: 11
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Post-bronchodilator FEV1
Hide Description Mean change from baseline during the treatment period in post-bronchodilator FEV1 [L]
Time Frame Change from baseline over 24 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis. Number of participants analyzed = number of participants with data available.
Arm/Group Title Roflumilast Placebo
Hide Arm/Group Description:
Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Overall Number of Participants Analyzed 452 460
Least Squares Mean (Standard Error)
Unit of Measure: mL
68  (9) 8  (9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roflumilast, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No adjustment of the significance level (0.05) was done as a hierarchical approach for hypotheses testing was used.
Method ANCOVA
Comments Repeated measurements analysis (change from baseline over 24 weeks of treatment taking all post-randomization measurements into account).
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 60
Confidence Interval (2-Sided) 95%
38 to 82
Parameter Dispersion
Type: Standard Error of the mean
Value: 11
Estimation Comments [Not Specified]
3.Secondary Outcome
Title COPD Exacerbation Rate (Mild, Moderate or Severe)
Hide Description Mean rate of COPD exacerbations requiring rescue medication of 3 or more puffs/day on at least 2 consecutive days (=mild COPD exacerbations), or 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 [ATS / ERS 2005].
Time Frame 24 weeks treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis
Arm/Group Title Roflumilast Placebo
Hide Arm/Group Description:
Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Overall Number of Participants Analyzed 466 467
Mean (95% Confidence Interval)
Unit of Measure: exacerbations per patient per year
1.9
(1.5 to 2.5)
2.4
(1.9 to 3.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roflumilast, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1408
Comments No adjustment of the significance level (0.05) was done as a hierarchical approach for hypotheses testing was used.
Method Poisson regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.58 to 1.08
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Transition Dyspnea Index (TDI) Focal Score
Hide Description 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.
Time Frame Change from baseline over 24 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis. Number of participants analyzed = number of participants with data available.
Arm/Group Title Roflumilast Placebo
Hide Arm/Group Description:
Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Overall Number of Participants Analyzed 454 460
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
1.2  (0.1) 1.1  (0.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roflumilast, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4654
Comments No adjustment of the significance level (0.05) was done as a hierarchical approach for hypotheses testing was used.
Method ANCOVA
Comments Repeated measurements analysis (change from baseline over 24 weeks of treatment taking all post-randomization measurements into account).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.2 to 0.4
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Shortness of Breath Questionnaire (SOBQ) Total Score
Hide Description 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".
Time Frame Change from baseline over 24 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis. Number of participants analyzed = number of participants with data available.
Arm/Group Title Roflumilast Placebo
Hide Arm/Group Description:
Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Overall Number of Participants Analyzed 454 461
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-0.6  (0.7) -1.1  (0.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roflumilast, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5457
Comments No adjustment of the significance level (0.05) was done as a hierarchical approach for hypotheses testing was used.
Method ANCOVA
Comments Repeated measurements analysis (change from baseline over 24 weeks of treatment taking all post-randomization measurements into account).
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-1.2 to 2.2
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.9
Estimation Comments [Not Specified]
Time Frame 24 weeks treatment period
Adverse Event Reporting Description The Safety Set was based on all randomized patients who took at least one dose of the investigational drug after randomization.
 
Arm/Group Title Roflumilast Placebo
Hide Arm/Group Description Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
All-Cause Mortality
Roflumilast Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Roflumilast Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   36/466 (7.73%)      42/467 (8.99%)    
Blood and lymphatic system disorders     
Anaemia  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Cardiac disorders     
Myocardial infarction  1  2/466 (0.43%)  2 1/467 (0.21%)  1
Atrial fibrillation  1  2/466 (0.43%)  2 0/467 (0.00%)  0
Cardiac failure  1  0/466 (0.00%)  0 2/467 (0.43%)  2
Acute myocardial infarction  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Angina pectoris  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Atrioventricular block complete  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Cardiac failure congestive  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Tachycardia  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Congenital, familial and genetic disorders     
Retinitis pigmentosa  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Ear and labyrinth disorders     
Tympanic membrane perforation  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Vertigo  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Gastrointestinal disorders     
Crohn's disease  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Diarrhoea  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Haematemesis  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Oesophageal varices haemorrhage  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Peptic ulcer perforation  1  0/466 (0.00%)  0 1/467 (0.21%)  1
General disorders     
Asthenia  1  1/466 (0.21%)  1 0/467 (0.00%)  0
General physical health deterioration  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Hyperthermia  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Nodule  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Pyrexia  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Infections and infestations     
Pneumonia  1  1/466 (0.21%)  1 2/467 (0.43%)  2
Abdominal abscess  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Bronchopneumonia  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Cellulitis  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Gastroenteritis  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Lobar pneumonia  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Tooth abscess  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Urinary tract infection  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Injury, poisoning and procedural complications     
Fracture  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Injury  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Radius fracture  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Investigations     
Investigation  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Weight decreased  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Metabolism and nutrition disorders     
Anorexia  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostate cancer  1  1/466 (0.21%)  1 2/467 (0.43%)  2
Colon cancer  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Fibroadenoma of breast  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Gastric cancer  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Pancreatic carcinoma metastatic  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Papillary thyroid cancer  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Renal neoplasm  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Small cell lung cancer stage unspecified  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Squamous cell carcinoma  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Nervous system disorders     
Carotid artery stenosis  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Cerebrovascular accident  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Loss of consciousness  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Meningorrhagia  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Psychiatric disorders     
Mental disorder  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Suicide attempt  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Renal and urinary disorders     
Renal failure acute  1  1/466 (0.21%)  1 2/467 (0.43%)  2
Renal failure  1  0/466 (0.00%)  0 2/467 (0.43%)  2
Dysuria  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Urinary tract obstruction  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  7/466 (1.50%)  7 11/467 (2.36%)  11
Acute respiratory failure  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Bronchospasm  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Foreign body aspiration  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Pleural effusion  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Skin and subcutaneous tissue disorders     
Rash papular  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Skin lesion  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Surgical and medical procedures     
Finger amputation  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Vascular disorders     
Aortic aneurysm  1  2/466 (0.43%)  2 1/467 (0.21%)  1
Intermittent claudication  1  1/466 (0.21%)  1 1/467 (0.21%)  1
Arterial occlusive disease  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Arterial restenosis  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Hypertension  1  0/466 (0.00%)  0 1/467 (0.21%)  1
Peripheral ischaemia  1  1/466 (0.21%)  1 0/467 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Roflumilast Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   165/466 (35.41%)      143/467 (30.62%)    
Gastrointestinal disorders     
Diarrhoea  1 [1]  38/466 (8.15%)  41 15/467 (3.21%)  16
Nausea  1  25/466 (5.36%)  26 1/467 (0.21%)  1
Infections and infestations     
Nasopharyngitis  1  33/466 (7.08%)  39 35/467 (7.49%)  43
Investigations     
Weight decreased  1 [1]  39/466 (8.37%)  39 5/467 (1.07%)  5
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1 [1]  70/466 (15.02%)  81 103/467 (22.06%)  126
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.0)
[1]
non-serious
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The study results may be published and/or presented at scientific meetings. Prior to any submission, all manuscripts/abstracts must be presented to the sponsor for possible comments.
Results Point of Contact
Name/Title: AstraZeneca Clinical Study Information Center
Organization: AstraZeneca
Phone: 1-877-240-9479
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00313209     History of Changes
Other Study ID Numbers: BY217/M2-127
2005-005080-28 ( EudraCT Number )
First Submitted: April 11, 2006
First Posted: April 12, 2006
Results First Submitted: March 17, 2011
Results First Posted: May 19, 2011
Last Update Posted: December 14, 2016