Trial to Assess the Anti-inflammatory Effects of Roflumilast in Chronic Obstructive Pulmonary Disease

• Additional cell count in biopsied material (sub-mucosa and epithelium) [cells/mm2] [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
• Total and differential cell counts in induced sputum [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
• Concentration of inflammatory biomarkers in sputum [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  Explorative examination of inflammatory parameter in sputum using the 46-biomarker Multi-Analyte Profiling (MAP) technology (Human InflammationMAP® v.1, Rules-Based Medicine, Inc., Austin, TX, U.S.A.)
• Concentration of inflammatory biomarkers in blood serum [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  Explorative examination of inflammatory parameter in blood serum using the 46-biomarker Multi-Analyte Profiling (MAP) technology (Human InflammationMAP® v.1, Rules-Based Medicine, Inc., Austin, TX, U.S.A.)
• Pulmonary function changes in the course of the trial [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  1. Forced expiratory volume in the first 1 second (FEV1 [L])
  2. Forced vital capacity (FVC [L])
  3. FEV1/FVC [%]

The objective of the Biopsy trial is to investigate the effect of roflumilast 500 µg tablets once daily versus placebo on inflammation parameters in bronchial biopsy tissue specimen and additional in sputum and blood serum. Also data on safety status will be obtained.

Patients to be included required to have moderate to severe COPD associated with chronic bronchitis. The total duration of this randomized, multicentre, phase III trial is 24 weeks maximum.

• COPD
• Chronic Obstructive Pulmonary Disease

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

• Active Comparator: Roflumilast
  Intervention: Drug: Roflumilast
• Active Comparator: Placebo
  Intervention: Drug: Placebo

Major Inclusion Criteria:

• Giving written informed consent
• History of COPD (according to GOLD 2009) for at least 12 months prior to baseline visit V0 associated with chronic productive cough for at least three months in each of the two years prior to baseline visit V0 (with other causes of productive cough excluded)
• Outpatients 40-80 years of age
• Post-bronchodilator 30% ≤FEV1 ≤80% predicted
• Post-bronchodilator FEV1/FVC ratio ≤70%
• Current or former smokers with smoking history ≥20 pack years

Main Exclusion Criteria:

• Criteria affecting the read-out parameters of the trial:

• Clinical instability, defined as experiencing a COPD exacerbation six months prior to V0
• An upper/lower respiratory tract infection which has not resolved four weeks prior to V0
• Diagnosis of asthma and/or other relevant lung disease
• Known alpha-1-antitrypsin deficiency
• Suspicion or diagnosis of a bleeding disorders irrespective of its pathophysiological mechanism
• Other protocol-defined exclusion criteria may apply