Phase 3
N=158
Trial to Assess the Anti-inflammatory Effects of Roflumilast in Chronic Obstructive Pulmonary Disease
COPD · Chronic Obstructive Pulmonary Disease
Bottom Line
View on ClinicalTrials.gov: NCT01509677 ↗Enrolled (actual)
158
Serious AEs
8.2%
Results posted
Nov 2019
Primary outcome: Primary: Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue. — 442.4; 427.1 CD8+ cells count
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Roflumilast (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- AstraZeneca
- Primary completion
- Feb 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue. |
442.4; 427.1 | — |
| PRIMARY Change in Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue |
13.4; 29.4 | 0.7922 |
| SECONDARY CD68+ Count in Biopsied Material (Submucosa) |
149.1; 124.4 | 0.7145 |
| SECONDARY CD68+ Cell Count in Biopsied Material (Submucosa): Poisson Regression (Ratio) |
126.8; 121.6 | 0.7136 |
| SECONDARY Change From V2 to V6 in CD68+ Cell Count (Cells/mm^2) in Biopsied Material (Submucosa) (ITT) |
6.1; -5.3 | 0.4606 |
| SECONDARY CD4+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model |
304.6; 255.0 | 0.2744 |
| SECONDARY CD45+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model |
818.4; 960.3 | 0.1128 |
| SECONDARY Neutrophils Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model |
118.6; 127.7 | 0.6740 |
| SECONDARY CD8+ Cell Count in Biopsied Material (Bronchial Epithelium): Poisson Regression Model |
422.1; 505.3 | 0.0677 |
| SECONDARY CD68+ Cell Count in Biopsied Material (Bronchial Epithelium):Poisson Regression Model |
76.3; 93.1 | 0.3566 |
| SECONDARY Change From V1 to V5 in Absolute Cell Count in Induced Sputum (10^6 Neutrophils/mL): Between-Treatment Difference |
1.7181; 0.0827 | 0.4794 |
| SECONDARY Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Macrophages/mL): Between-Treatment Difference |
0.1017; -0.3710 | 0.1541 |
| SECONDARY Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Eosinophils/mL): Between-Treatment Difference |
-0.0986; -0.0360 | 0.0927 |
| SECONDARY Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Lymphocytes/mL): Between-Treatment Difference |
-0.0167; -0.0060 | 0.5175 |
| SECONDARY Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Neutrophils/mL) |
2.527; 0.382 | 0.5205 |
| SECONDARY Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Macrophages/mL) |
0.315; -0.826 | 0.7052 |
| SECONDARY Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Eosinophils/mL) |
-1.826; -0.041 | 0.0127 sig |
| SECONDARY Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Lymphocytes)/mL) |
-0.137; -0.086 | 0.7862 |
| SECONDARY Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (Alfa- 2-Macroglobulin (µg/mL)) |
-0.32; -0.48 | 0.8769 |
| SECONDARY Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (IL-8 (pg/mL)) |
-827.3; -1538.4 | 0.7978 |
| SECONDARY Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (MMP Type 9 (ng/mL)) |
80.1; -8.4 | 0.2669 |
| SECONDARY Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (MCP-1 (pg/mL)) |
-95.2; -69.3 | 0.7033 |
| SECONDARY Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (TIMP-1 (ng/mL)) |
25.87; -1.92 | 0.1264 |
| SECONDARY Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (VEGF (pg/mL)) |
253.1; -43.7 | 0.0185 sig |
| SECONDARY Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (Alfa-2-Macroglobulin (µg/mL)) |
-0.05; -0.05 | 0.9989 |
| SECONDARY Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (IL-8 (pg/mL)) |
-4.48; -3.92 | 0.6701 |
| SECONDARY Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (MMP Type 9 (ng/mL)) |
0.8; -1.0 | 0.1105 |
| SECONDARY Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (MCP-1(pg/mL)) |
-24.8; -23.4 | 0.9261 |
| SECONDARY Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (TIMP-1(ng/mL)) |
2.7; -7.5 | 0.0257 sig |
| SECONDARY Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (VEGF(pg/mL)) |
11.3; -21.5 | 0.0728 |
| SECONDARY Change From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FEV1 (L)) |
0.028; -0.035 | 0.0380 sig |
| SECONDARY Change From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FVC (L)) |
0.031; -0.033 | 0.2482 |
| SECONDARY Wicoxon Signed-rank Test for Change From V2 to V6 in Post-bronchodilator FEV1/FVC |
0.5; -0.5 | 0.2629 |
Summary
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01509677). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.