This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00313209
First received: April 11, 2006
Last updated: November 1, 2016
Last verified: November 2016
Results First Received: March 17, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Participant, Investigator);   Primary Purpose: Treatment
Condition: Chronic Obstructive Pulmonary Disease (COPD)
Interventions: Drug: Roflumilast
Drug: Placebo

  Participant Flow
  Hide Participant Flow

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
  Hide Baseline Characteristics

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 
Overall Participants Analyzed 
[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]
Count of Participants
     
Female      147  31.5%      168  36.0%      315  33.8% 
Male      319  68.5%      299  64.0%      618  66.2% 


  Outcome Measures
  Hide All Outcome Measures

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

Measure Type Primary
Measure Title Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1)
Measure Description Mean change from baseline during the treatment period in pre-bronchodilator FEV1 [L]
Time Frame Change from baseline over 24 weeks of treatment  

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

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

Measured Values
   Roflumilast   Placebo 
Participants Analyzed 
[Units: Participants]
 456   463 
Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) 
[Units: mL]
Least Squares Mean (Standard Error)
 39  (9)   -10  (9) 


Statistical Analysis 1 for Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] ANCOVA
P Value [4] <0.0001
Mean Difference (Net) [5] 49
95% Confidence Interval 27 to 71
Standard Error of the mean (11)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Repeated measurements analysis (change from baseline over 24 weeks of treatment taking all post-randomization measurements into account).
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No adjustment of the significance level (0.05) was done as a hierarchical approach for hypotheses testing was used.
[5] Other relevant estimation information:
  No text entered.



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

Measure Type Secondary
Measure Title Post-bronchodilator FEV1
Measure Description Mean change from baseline during the treatment period in post-bronchodilator FEV1 [L]
Time Frame Change from baseline over 24 weeks of treatment  

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

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

Measured Values
   Roflumilast   Placebo 
Participants Analyzed 
[Units: Participants]
 452   460 
Post-bronchodilator FEV1 
[Units: mL]
Least Squares Mean (Standard Error)
 68  (9)   8  (9) 


Statistical Analysis 1 for Post-bronchodilator FEV1
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] ANCOVA
P Value [4] <0.0001
Mean Difference (Net) [5] 60
95% Confidence Interval 38 to 82
Standard Error of the mean (11)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Repeated measurements analysis (change from baseline over 24 weeks of treatment taking all post-randomization measurements into account).
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No adjustment of the significance level (0.05) was done as a hierarchical approach for hypotheses testing was used.
[5] Other relevant estimation information:
  No text entered.



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

Measure Type Secondary
Measure Title COPD Exacerbation Rate (Mild, Moderate or Severe)
Measure 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  

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.
ITT analysis

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

Measured Values
   Roflumilast   Placebo 
Participants Analyzed 
[Units: Participants]
 466   467 
COPD Exacerbation Rate (Mild, Moderate or Severe) 
[Units: Exacerbations per patient per year]
Mean (95% Confidence Interval)
 1.9 
 (1.5 to 2.5) 
 2.4 
 (1.9 to 3.1) 


Statistical Analysis 1 for COPD Exacerbation Rate (Mild, Moderate or Severe)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Poisson regression
P Value [4] 0.1408
Rate ratio [5] 0.79
95% Confidence Interval 0.58 to 1.08
Standard Error of the mean (0.12)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No adjustment of the significance level (0.05) was done as a hierarchical approach for hypotheses testing was used.
[5] Other relevant estimation information:
  No text entered.



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

Measure Type Secondary
Measure Title Transition Dyspnea Index (TDI) Focal Score
Measure 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  

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

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

Measured Values
   Roflumilast   Placebo 
Participants Analyzed 
[Units: Participants]
 454   460 
Transition Dyspnea Index (TDI) Focal Score 
[Units: Scores on a scale]
Least Squares Mean (Standard Error)
 1.2  (0.1)   1.1  (0.1) 


Statistical Analysis 1 for Transition Dyspnea Index (TDI) Focal Score
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] ANCOVA
P Value [4] 0.4654
Mean Difference (Final Values) [5] 0.1
95% Confidence Interval -0.2 to 0.4
Standard Error of the mean (0.2)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Repeated measurements analysis (change from baseline over 24 weeks of treatment taking all post-randomization measurements into account).
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No adjustment of the significance level (0.05) was done as a hierarchical approach for hypotheses testing was used.
[5] Other relevant estimation information:
  No text entered.



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

Measure Type Secondary
Measure Title Shortness of Breath Questionnaire (SOBQ) Total Score
Measure 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  

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

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

Measured Values
   Roflumilast   Placebo 
Participants Analyzed 
[Units: Participants]
 454   461 
Shortness of Breath Questionnaire (SOBQ) Total Score 
[Units: Scores on a scale]
Least Squares Mean (Standard Error)
 -0.6  (0.7)   -1.1  (0.7) 


Statistical Analysis 1 for Shortness of Breath Questionnaire (SOBQ) Total Score
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] ANCOVA
P Value [4] 0.5457
Mean Difference (Net) [5] 0.5
95% Confidence Interval -1.2 to 2.2
Standard Error of the mean (0.9)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Repeated measurements analysis (change from baseline over 24 weeks of treatment taking all post-randomization measurements into account).
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No adjustment of the significance level (0.05) was done as a hierarchical approach for hypotheses testing was used.
[5] Other relevant estimation information:
  No text entered.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information