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

• Post-bronchodilator FEV1 [ Time Frame: Change from baseline over 24 weeks of treatment ] [ Designated as safety issue: No ]
  Mean change from baseline during the treatment period in post-bronchodilator FEV1 [L]
• COPD Exacerbation Rate (Mild, Moderate or Severe) [ Time Frame: 24 weeks treatment period ] [ Designated as safety issue: No ]

  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].

• Transition Dyspnea Index (TDI) Focal Score [ Time Frame: Change from baseline over 24 weeks of treatment ] [ Designated as safety issue: No ]

  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.

• Shortness of Breath Questionnaire (SOBQ) Total Score [ Time Frame: Change from baseline over 24 weeks of treatment ] [ Designated as safety issue: No ]

  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".

• Other spirometry parameters
• COPD symptoms
• safety and tolerability.

The aim of the study is to compare the efficacy of roflumilast on pulmonary function and symptomatic parameters in patients with chronic obstructive pulmonary disease (COPD) during concomitant administration of salmeterol. The study duration will last up to 28 weeks. The study will provide further data on safety and tolerability of roflumilast.

• Drug: Roflumilast
  500 µg, once daily, oral administration in the morning
• Drug: Placebo
  once daily

• Active Comparator: Roflumilast

  Roflumilast 500 µg

  underlying medication: salmeterol 50 μg, twice daily, inhaled

  Intervention: Drug: Roflumilast
• Placebo Comparator: Placebo

  Placebo

  underlying medication: salmeterol 50 μg, twice daily, inhaled

  Intervention: Drug: Placebo

Main Inclusion Criteria:

• History of COPD for at least 12 months prior to baseline visit
• FEV1/FVC ratio (post-bronchodilator) ≤ 70%
• FEV1 (post-bronchodilator) between ≥ 40% and ≤ 70% of predicted

Main Exclusion Criteria:

• COPD exacerbation indicated by a treatment with systemic glucocorticosteroids and/or antibiotics not stopped at least 4 weeks prior to baseline visit