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

This study has been completed.
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT00313209
First received: April 11, 2006
Last updated: May 4, 2012
Last verified: April 2011
Results First Received: March 17, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Chronic Obstructive Pulmonary Disease (COPD)
Interventions: Drug: Roflumilast
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Roflumilast Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Placebo Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled

Participant Flow:   Overall Study
    Roflumilast     Placebo  
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.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Roflumilast Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Placebo Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Total Total of all reporting groups

Baseline Measures
    Roflumilast     Placebo     Total  
Number of Participants  
[units: participants]
  466     467     933  
Age  
[units: years]
Mean ± Standard Deviation
  64.9  ± 8.7     64.9  ± 9.3     64.9  ± 9.0  
Gender  
[units: participants]
     
Female     147     168     315  
Male     319     299     618  



  Outcome Measures
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1.  Primary:   Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1)   [ Time Frame: Change from baseline over 24 weeks of treatment ]

2.  Secondary:   Post-bronchodilator FEV1   [ Time Frame: Change from baseline over 24 weeks of treatment ]

3.  Secondary:   COPD Exacerbation Rate (Mild, Moderate or Severe)   [ Time Frame: 24 weeks treatment period ]

4.  Secondary:   Transition Dyspnea Index (TDI) Focal Score   [ Time Frame: Change from baseline over 24 weeks of treatment ]

5.  Secondary:   Shortness of Breath Questionnaire (SOBQ) Total Score   [ Time Frame: Change from baseline over 24 weeks of treatment ]


  Serious Adverse Events
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Time Frame 24 weeks treatment period
Additional Description The Safety Set was based on all randomized patients who took at least one dose of the investigational drug after randomization.

Reporting Groups
  Description
Roflumilast Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Placebo Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled

Serious Adverse Events
    Roflumilast     Placebo  
Total, serious adverse events      
# participants affected / at risk     36/466 (7.73%)     42/467 (8.99%)  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Cardiac disorders      
Myocardial infarction † 1    
# participants affected / at risk     2/466 (0.43%)     1/467 (0.21%)  
# events     2     1  
Atrial fibrillation † 1    
# participants affected / at risk     2/466 (0.43%)     0/467 (0.00%)  
# events     2     0  
Cardiac failure † 1    
# participants affected / at risk     0/466 (0.00%)     2/467 (0.43%)  
# events     0     2  
Acute myocardial infarction † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Angina pectoris † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Atrioventricular block complete † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Cardiac failure congestive † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Tachycardia † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Congenital, familial and genetic disorders      
Retinitis pigmentosa † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Ear and labyrinth disorders      
Tympanic membrane perforation † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Vertigo † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Gastrointestinal disorders      
Crohn's disease † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Diarrhoea † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Haematemesis † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Oesophageal varices haemorrhage † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Peptic ulcer perforation † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
General disorders      
Asthenia † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
General physical health deterioration † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Hyperthermia † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Nodule † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Pyrexia † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Infections and infestations      
Pneumonia † 1    
# participants affected / at risk     1/466 (0.21%)     2/467 (0.43%)  
# events     1     2  
Abdominal abscess † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Bronchopneumonia † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Cellulitis † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Gastroenteritis † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Lobar pneumonia † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Tooth abscess † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Urinary tract infection † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Injury, poisoning and procedural complications      
Fracture † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Injury † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Radius fracture † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Investigations      
Investigation † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Weight decreased † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Metabolism and nutrition disorders      
Anorexia † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Prostate cancer † 1    
# participants affected / at risk     1/466 (0.21%)     2/467 (0.43%)  
# events     1     2  
Colon cancer † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Fibroadenoma of breast † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Gastric cancer † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Pancreatic carcinoma metastatic † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Papillary thyroid cancer † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Renal neoplasm † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Small cell lung cancer stage unspecified † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Squamous cell carcinoma † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Nervous system disorders      
Carotid artery stenosis † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Cerebrovascular accident † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Loss of consciousness † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Meningorrhagia † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Psychiatric disorders      
Mental disorder † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Suicide attempt † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Renal and urinary disorders      
Renal failure acute † 1    
# participants affected / at risk     1/466 (0.21%)     2/467 (0.43%)  
# events     1     2  
Renal failure † 1    
# participants affected / at risk     0/466 (0.00%)     2/467 (0.43%)  
# events     0     2  
Dysuria † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Urinary tract obstruction † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Reproductive system and breast disorders      
Benign prostatic hyperplasia † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Respiratory, thoracic and mediastinal disorders      
Chronic obstructive pulmonary disease † 1    
# participants affected / at risk     7/466 (1.50%)     11/467 (2.36%)  
# events     7     11  
Acute respiratory failure † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Bronchospasm † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Foreign body aspiration † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Pleural effusion † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Skin and subcutaneous tissue disorders      
Rash papular † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Skin lesion † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Surgical and medical procedures      
Finger amputation † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Vascular disorders      
Aortic aneurysm † 1    
# participants affected / at risk     2/466 (0.43%)     1/467 (0.21%)  
# events     2     1  
Intermittent claudication † 1    
# participants affected / at risk     1/466 (0.21%)     1/467 (0.21%)  
# events     1     1  
Arterial occlusive disease † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Arterial restenosis † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Hypertension † 1    
# participants affected / at risk     0/466 (0.00%)     1/467 (0.21%)  
# events     0     1  
Peripheral ischaemia † 1    
# participants affected / at risk     1/466 (0.21%)     0/467 (0.00%)  
# events     1     0  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (11.0)




  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Respiratory Medical Advisor
Organization: Nycomed GmbH
phone: 0049-7531-840
e-mail: clinicaltrials@nycomed.com


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Publications automatically indexed to this study:

Responsible Party: Nycomed
ClinicalTrials.gov Identifier: NCT00313209     History of Changes
Other Study ID Numbers: BY217/M2-127, 2005-005080-28
Study First Received: April 11, 2006
Results First Received: March 17, 2011
Last Updated: May 4, 2012
Health Authority: Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Netherlands: Medicines Evaluation Board (MEB)
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency