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CompletedNCT01509677Updated Nov 29, 2019Results posted

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

A Phase 3 interventional study of Roflumilast and Placebo in COPD and Chronic Obstructive Pulmonary Disease, sponsored by AstraZeneca. Completed at 20 sites in 5 countries. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2019-11-29.

Sponsored by AstraZeneca · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
158
Allocation
Randomized
Ages
40 Years to 80 Years
Sex
All
01

Study 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.

Read the detailed description

This was a multicenter, double-blind, randomized, parallel group, phase 3 study. Patients included had a history of COPD (GOLD stage II-III, in Germany stage II only) with chronic productive cough.

There were 2 parallel treatment arms (placebo and roflumilast 500 μg once daily). A 1 to 1 randomization scheme was used, that is, patients were allocated to roflumilast 500 μg or placebo in equal proportions. Randomization was stratified by concomitant LABA use.

The total duration of this study was 24 weeks maximum per patient. The study consisted of the following periods:

  • Single-blind placebo run-in period (6 weeks) with visits at Week -6 (visit 0 [V0]), Week -2 (V1), and Week 0 (V2, randomization visit), during which all patients received placebo.
  • Double-blind treatment period (16 weeks) during which patients received either roflumilast or matching placebo with visits at Week 6 (V4), Week 14 (V5), and Week 16 (V6).

An additional visit (V3) within 2 weeks after bronchoscopy/bronchial biopsy was performed purely as a safety visit. The exact timing of this safety visit was to be determined by the investigator. Safety follow-up. All AEs were followed up to 30 days after the double-blind treatment period. An additional safety visit, V7, was scheduled within 2 weeks after the second bronchoscopy. The exact timing of the safety visit was to be determined by the investigator.

Patients were required not to take any food or drink overnight for at least 8 hours prior to returning to the study center for each visit. Patients were also asked to avoid strenuous exercise for 8 hours prior to each study visit and to avoid smoking for 4 hours prior to each study visit.

For visits where patients did not undergo blood collections or biopsies, the fasting requirement was only mandated if clinically indicated, per investigator judgment.

02

Conditions studied

  • COPD
  • Chronic Obstructive Pulmonary Disease

Keywords

  • Roflumilast
  • Chronic Obstructive Pulmonary Disease
  • COPD
03

In context

Pulmonary Disease, Chronic Obstructive

4,252 studies on the registry are indexed under Pulmonary Disease, Chronic Obstructive; 707 are open to participants now.

This study's enrollment of 158 is above the median of 70 across 3,008 interventional studies indexed under Pulmonary Disease, Chronic Obstructive.

Browse Pulmonary Disease, Chronic Obstructive studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,492 studies on the registry; 266 are open to participants now.

Of its 368 completed or terminated interventional studies of FDA-regulated products, 176 (48%) have results posted.

Browse AstraZeneca studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
158 participants (actual)

Study arms

  • Active comparator
    Roflumilast

    500 μg tablet, once daily, oral administration in the morning after breakfast

    Drug: Roflumilast

  • Placebo comparator
    Placebo

    tablet, once daily, oral administration in the morning after breakfast

    Drug: Placebo

Interventions

  • DrugRoflumilast

    500 μg tablet, once daily, oral administration in the morning after breakfast

    Also known as: Daxas

  • DrugPlacebo

    tablet, once daily, oral administration in the morning after breakfast

    Also known as: Placebo to Roflumilast

06

What researchers measure

Primary outcomes

  1. Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue.

    Time frame: 16 weeks

  2. Change in Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue

    Time frame: Baseline to 16 weeks

Secondary outcomes

  1. CD68+ Count in Biopsied Material (Submucosa)

    Time frame: 16 weeks

  2. CD68+ Cell Count in Biopsied Material (Submucosa): Poisson Regression (Ratio)

    CD68+ Cell Count in Biopsied Material (submucosa): Poisson regression (ratio). Clarification: Measure type described as "Number" refers to "Risk of each treatment group". It is not possible to select "risk" from this template so "number" was selected instead. This issue applies to similar variables reporting poisson regression.

    Time frame: 16 weeks

  3. Change From V2 to V6 in CD68+ Cell Count (Cells/mm^2) in Biopsied Material (Submucosa) (ITT)

    Time frame: Baseline and 16 weeks

  4. CD4+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model

    CD4+ Cell Counts in biopsied Material (submucosa):poisson regression model. Clarification: Measure type "Number" refers to "Risk of each treatment group".

    Time frame: 16 weeks

  5. CD45+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model

    CD45+ Cell Counts in biopsied Material (submucosa):poisson regression model. Clarification: Measure type "Number" refers to "treatment risk"

    Time frame: 16 weeks

  6. Neutrophils Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model

    Neutrophils Cell Counts in biopsied Material (submucosa):poisson regression model. Clarification: Measure type "Number" refers to "Treatment risk"

    Time frame: Baseline to 14 weeks

  7. CD8+ Cell Count in Biopsied Material (Bronchial Epithelium): Poisson Regression Model

    CD8+ Cell Count in biopsied material (Bronchial Epithelium): poisson regression model. Clarification: Measure Type "Number" refers to "Treatment risk"

    Time frame: 16 weeks

  8. CD68+ Cell Count in Biopsied Material (Bronchial Epithelium):Poisson Regression Model

    CD68+ Cell Count in biopsied material (Bronchial Epithelium):poisson regression model. Clarification: Measure type "Number" refers to "Treatment Risk"

    Time frame: 16 weeks

  9. Change From V1 to V5 in Absolute Cell Count in Induced Sputum (10^6 Neutrophils/mL): Between-Treatment Difference

    Time frame: Baseline to 14 weeks

  10. Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Macrophages/mL): Between-Treatment Difference

    Time frame: Baseline to 14 weeks

  11. Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Eosinophils/mL): Between-Treatment Difference

    Time frame: Baseline to 14 weeks

  12. Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Lymphocytes/mL): Between-Treatment Difference

    Time frame: BAseline to 14 weeks

  13. Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Neutrophils/mL)

    Time frame: Baseline to 14 weeks

  14. Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Macrophages/mL)

    Time frame: Baseline to 14 weeks

  15. Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Eosinophils/mL)

    Time frame: Baseline to 14 weeks

  16. Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Lymphocytes)/mL)

    Time frame: Baseline to 14 weeks

  17. Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (Alfa- 2-Macroglobulin (µg/mL))

    Time frame: Baseline to 14 weeks

  18. Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (IL-8 (pg/mL))

    Time frame: Baseline to 14 weeks

  19. Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (MMP Type 9 (ng/mL))

    Time frame: Baseline to 14 weeks

  20. Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (MCP-1 (pg/mL))

    Time frame: Baseline to 14 weeks

  21. Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (TIMP-1 (ng/mL))

    Time frame: Baseline to 14 weeks

  22. Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (VEGF (pg/mL))

    Time frame: Baseline to 14 weeks

  23. Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (Alfa-2-Macroglobulin (µg/mL))

    Time frame: Baseline to 14 weeks

  24. Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (IL-8 (pg/mL))

    Time frame: Baseline to 14 weeks

  25. Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (MMP Type 9 (ng/mL))

    Time frame: Baseline to 14 weeks

  26. Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (MCP-1(pg/mL))

    Time frame: Baseline to 14 weeks

  27. Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (TIMP-1(ng/mL))

    Time frame: Baseline to 14 weeks

  28. Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (VEGF(pg/mL))

    Time frame: Baseline to 14 weeks

  29. Change From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FEV1 (L))

    Time frame: Baseline to 16 weeks

  30. Change From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FVC (L))

    Time frame: Baseline to 16 weeks

  31. Wicoxon Signed-rank Test for Change From V2 to V6 in Post-bronchodilator FEV1/FVC

    Wilcoxon test is a non-parametric test to evaluate differences among treatments in the variable that is being reported here. The data reported in the outcome measure data table are hodges Lehmann estimate of change from baseline in FEV1/FVC ratio.

    Time frame: Baseline to 16 weeks

07

Results

Posted Nov 29, 2019

Participant flow

Participant flow — Overall Study
MilestoneR500Placebo
Started7979
Completed7673
Not completed36

Outcome measures

PrimaryNumber of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue.
Time frame:
16 weeks
Reported as:
Mean · CD8+ cells count
Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue.
CD8+ cells countR500Placebo
Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue.442.4 ± 312.74427.1 ± 261.42
PrimaryChange in Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue
Time frame:
Baseline to 16 weeks
Reported as:
Mean · cells/mm^2
Change in Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue
cells/mm^2R500Placebo
Change in Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue13.4 ± 302.6929.4 ± 298.88
Statistical analysis
  • R500 vs Placebo · Poisson regression model · p = 0.7922 (This is p-value testing significance of "treatment" effect)
  • R500 vs Placebo · Poisson regression model · p = 0.7917 · Risk ratio (rr): 1.03 · 95% CI 0.82 to 1.30
SecondaryCD68+ Count in Biopsied Material (Submucosa)
Time frame:
16 weeks
Reported as:
Mean · CD68+ Count
CD68+ Count in Biopsied Material (Submucosa)
CD68+ CountR500Placebo
CD68+ Count in Biopsied Material (Submucosa)149.1 ± 113.91124.4 ± 93.15
Statistical analysis
  • R500 vs Placebo · Poisson regression model · p = 0.7145 (This is p-value testing significance of "treatment" effect)
SecondaryCD68+ Cell Count in Biopsied Material (Submucosa): Poisson Regression (Ratio)

CD68+ Cell Count in Biopsied Material (submucosa): Poisson regression (ratio). Clarification: Measure type described as "Number" refers to "Risk of each treatment group". It is not possible to select "risk" from this template so "number" was selected instead. This issue applies to similar variables reporting poisson regression.

Time frame:
16 weeks
Reported as:
Number · CD68+ Cell Count
CD68+ Cell Count in Biopsied Material (Submucosa): Poisson Regression (Ratio)
CD68+ Cell CountR500Placebo
CD68+ Cell Count in Biopsied Material (Submucosa): Poisson Regression (Ratio)126.8 ± NA121.6 ± NA
Statistical analysis
  • R500 vs Placebo · Poisson regression model · p = 0.7136 · Risk ratio (rr): 1.04 · 95% CI 0.83 to 1.30
SecondaryChange From V2 to V6 in CD68+ Cell Count (Cells/mm^2) in Biopsied Material (Submucosa) (ITT)
Time frame:
Baseline and 16 weeks
Reported as:
Least squares mean · CD68+ Cell Count (cells/mm^2)
Change From V2 to V6 in CD68+ Cell Count (Cells/mm^2) in Biopsied Material (Submucosa) (ITT)
CD68+ Cell Count (cells/mm^2)R500Placebo
Change From V2 to V6 in CD68+ Cell Count (Cells/mm^2) in Biopsied Material (Submucosa) (ITT)6.1 ± 10.99-5.3 ± 11.05
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.4606 · Mean difference (final values): 11.4 · 95% CI -19.2 to 42.1
SecondaryCD4+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model

CD4+ Cell Counts in biopsied Material (submucosa):poisson regression model. Clarification: Measure type "Number" refers to "Risk of each treatment group".

Time frame:
16 weeks
Reported as:
Number · CD4+ Cell Counts
CD4+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model
CD4+ Cell CountsR500Placebo
CD4+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model304.6 ± NA255.0 ± NA
Statistical analysis
  • R500 vs Placebo · Poisson regression model · p = 0.2744 · Risk ratio (rr): 1.19 · 95% CI 0.87 to 1.64
SecondaryCD45+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model

CD45+ Cell Counts in biopsied Material (submucosa):poisson regression model. Clarification: Measure type "Number" refers to "treatment risk"

Time frame:
16 weeks
Reported as:
Number · CD45+ Cell Counts
CD45+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model
CD45+ Cell CountsR500Placebo
CD45+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model818.4 ± NA960.3 ± NA
Statistical analysis
  • R500 vs Placebo · Poisson regression model · p = 0.1128 · Risk ratio (rr): 0.85 · 95% CI 0.70 to 1.04
SecondaryNeutrophils Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model

Neutrophils Cell Counts in biopsied Material (submucosa):poisson regression model. Clarification: Measure type "Number" refers to "Treatment risk"

Time frame:
Baseline to 14 weeks
Reported as:
Number · Neutrophils Cell Counts
Neutrophils Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model
Neutrophils Cell CountsR500Placebo
Neutrophils Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model118.6 ± NA127.7 ± NA
Statistical analysis
  • R500 vs Placebo · Regression, Linear · p = 0.6740 · Risk ratio (rr): 0.93 · 95% CI 0.66 to 1.31Poisson regression model
SecondaryCD8+ Cell Count in Biopsied Material (Bronchial Epithelium): Poisson Regression Model

CD8+ Cell Count in biopsied material (Bronchial Epithelium): poisson regression model. Clarification: Measure Type "Number" refers to "Treatment risk"

Time frame:
16 weeks
Reported as:
Number · CD8+ Cell Count
CD8+ Cell Count in Biopsied Material (Bronchial Epithelium): Poisson Regression Model
CD8+ Cell CountR500Placebo
CD8+ Cell Count in Biopsied Material (Bronchial Epithelium): Poisson Regression Model422.1 ± NA505.3 ± NA
Statistical analysis
  • R500 vs Placebo · Poisson regression model · p = 0.0677 · Risk ratio (rr): 0.84 · 95% CI 0.69 to 1.01
SecondaryCD68+ Cell Count in Biopsied Material (Bronchial Epithelium):Poisson Regression Model

CD68+ Cell Count in biopsied material (Bronchial Epithelium):poisson regression model. Clarification: Measure type "Number" refers to "Treatment Risk"

Time frame:
16 weeks
Reported as:
Number · CD68+ Cell Count
CD68+ Cell Count in Biopsied Material (Bronchial Epithelium):Poisson Regression Model
CD68+ Cell CountR500Placebo
CD68+ Cell Count in Biopsied Material (Bronchial Epithelium):Poisson Regression Model76.3 ± NA93.1 ± NA
Statistical analysis
  • R500 vs Placebo · Poisson regression model · p = 0.3566 · Risk ratio (rr): 0.82 · 95% CI 0.54 to 1.25
SecondaryChange From V1 to V5 in Absolute Cell Count in Induced Sputum (10^6 Neutrophils/mL): Between-Treatment Difference
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · 10^6 neutrophils/mL
Change From V1 to V5 in Absolute Cell Count in Induced Sputum (10^6 Neutrophils/mL): Between-Treatment Difference
10^6 neutrophils/mLR500Placebo
Change From V1 to V5 in Absolute Cell Count in Induced Sputum (10^6 Neutrophils/mL): Between-Treatment Difference1.7181 ± 1.644710.0827 ± 1.61220
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.4794 · Mean difference (final values): 1.6354 · 95% CI -2.9429 to 6.2137
SecondaryChange From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Macrophages/mL): Between-Treatment Difference
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · 10^6 macrophages/mL
Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Macrophages/mL): Between-Treatment Difference
10^6 macrophages/mLR500Placebo
Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Macrophages/mL): Between-Treatment Difference0.1017 ± 0.23396-0.3710 ± 0.22970
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.1541 · Mean difference (final values): 0.4727 · 95% CI -0.1810 to 1.1264
SecondaryChange From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Eosinophils/mL): Between-Treatment Difference
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · 10^6 eosinophils/mL
Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Eosinophils/mL): Between-Treatment Difference
10^6 eosinophils/mLR500Placebo
Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Eosinophils/mL): Between-Treatment Difference-0.0986 ± 0.02639-0.0360 ± 0.02585
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.0927 · Mean difference (final values): -0.0626 · 95% CI -0.1358 to 0.0106
SecondaryChange From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Lymphocytes/mL): Between-Treatment Difference
Time frame:
BAseline to 14 weeks
Reported as:
Least squares mean · 10^6 lymphocytes/mL
Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Lymphocytes/mL): Between-Treatment Difference
10^6 lymphocytes/mLR500Placebo
Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Lymphocytes/mL): Between-Treatment Difference-0.0167 ± 0.01167-0.0060 ± 0.01141
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.5175 · Mean difference (final values): -0.0107 · 95% CI -0.0435 to 0.0220
SecondaryChange From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Neutrophils/mL)
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · 10^6 neutrophils/mL
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Neutrophils/mL)
10^6 neutrophils/mLR500Placebo
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Neutrophils/mL)2.527 ± 2.35710.382 ± 2.3535
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.5205 · Mean difference (final values): 2.146 · 95% CI -4.466 to 8.757
SecondaryChange From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Macrophages/mL)
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · 10^6 macrophages/mL
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Macrophages/mL)
10^6 macrophages/mLR500Placebo
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Macrophages/mL)0.315 ± 2.1328-0.826 ± 2.1316
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.7052 · Mean difference (final values): 1.141 · 95% CI -4.835 to 7.117
SecondaryChange From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Eosinophils/mL)
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · 10^6 eosinophils/m
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Eosinophils/mL)
10^6 eosinophils/mR500Placebo
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Eosinophils/mL)-1.826 ± 0.5214-0.041 ± 0.5200
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.0127 · Mean difference (final values): -1.867 · 95% CI -3.324 to -0.409
SecondaryChange From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Lymphocytes)/mL)
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · 10^6 lymphocytes)/mL
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Lymphocytes)/mL)
10^6 lymphocytes)/mLR500Placebo
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Lymphocytes)/mL)-0.137 ± 0.1332-0.086 ± 1.329
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.7862 · Mean difference (final values): -0.051 · 95% CI -0.423 to 0.321
SecondaryChange From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (Alfa- 2-Macroglobulin (µg/mL))
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · µg/mL
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (Alfa- 2-Macroglobulin (µg/mL))
µg/mLR500Placebo
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (Alfa- 2-Macroglobulin (µg/mL))-0.32 ± 0.730-0.48 ± 0.700
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.8769 · Mean difference (final values): 0.16 · 95% CI -1.84 to 2.15
SecondaryChange From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (IL-8 (pg/mL))
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · pg/mL
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (IL-8 (pg/mL))
pg/mLR500Placebo
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (IL-8 (pg/mL))-827.3 ± 1995.79-1538.4 ± 1941.08
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.7978 · Mean difference (final values): 711.1 · 95% CI -4778.3 to 6200.5
SecondaryChange From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (MMP Type 9 (ng/mL))
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · ng/mL
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (MMP Type 9 (ng/mL))
ng/mLR500Placebo
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (MMP Type 9 (ng/mL))80.1 ± 57.07-8.4 ± 55.44
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.2669 · Mean difference (final values): 88.5 · 95% CI -68.6 to 245.6
SecondaryChange From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (MCP-1 (pg/mL))
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · pg/mL
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (MCP-1 (pg/mL))
pg/mLR500Placebo
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (MCP-1 (pg/mL))-95.2 ± 49.23-69.3 ± 46.93
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.7033 · Mean difference (final values): -25.9 · 95% CI -160.3 to 108.5
SecondaryChange From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (TIMP-1 (ng/mL))
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · ng/mL
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (TIMP-1 (ng/mL))
ng/mLR500Placebo
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (TIMP-1 (ng/mL))25.87 ± 13.085-1.92 ± 12.551
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.1264 · Mean difference (final values): 27.79 · 95% CI -7.97 to 63.55
SecondaryChange From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (VEGF (pg/mL))
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · pg/mL
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (VEGF (pg/mL))
pg/mLR500Placebo
Change From Baseline of Concentration of Inflammatory Biomarkers in Induced Sputum: Primary Parameters of Interest (FAS) (VEGF (pg/mL))253.1 ± 89.46-43.7 ± 86.84
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.0185 · Mean difference (final values): 296.8 · 95% CI 50.9 to 542.7
SecondaryChange From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (Alfa-2-Macroglobulin (µg/mL))
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · µg/mL
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (Alfa-2-Macroglobulin (µg/mL))
µg/mLR500Placebo
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (Alfa-2-Macroglobulin (µg/mL))-0.05 ± 0.061-0.05 ± 0.062
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.9989 · Mean difference (final values): 0.00 · 95% CI -0.17 to 0.17
SecondaryChange From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (IL-8 (pg/mL))
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · pg/mL
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (IL-8 (pg/mL))
pg/mLR500Placebo
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (IL-8 (pg/mL))-4.48 ± 0.929-3.92 ± 0.945
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.6701 · Mean difference (final values): -0.56 · 95% CI -3.15 to 2.03
SecondaryChange From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (MMP Type 9 (ng/mL))
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · ng/mL
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (MMP Type 9 (ng/mL))
ng/mLR500Placebo
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (MMP Type 9 (ng/mL))0.8 ± 0.78-1.0 ± 0.79
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.1105 · Mean difference (final values): 1.8 · 95% CI -0.4 to 3.9
SecondaryChange From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (MCP-1(pg/mL))
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · pg/mL
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (MCP-1(pg/mL))
pg/mLR500Placebo
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (MCP-1(pg/mL))-24.8 ± 11.0-23.4 ± 11.21
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.9261 · Mean difference (final values): -1.5 · 95% CI -32.4 to 29.5
SecondaryChange From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (TIMP-1(ng/mL))
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · ng/mL
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (TIMP-1(ng/mL))
ng/mLR500Placebo
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (TIMP-1(ng/mL))2.7 ± 3.19-7.5 ± 3.25
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.0257 · Mean difference (final values): 10.1 · 95% CI 1.2 to 19.0
SecondaryChange From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (VEGF(pg/mL))
Time frame:
Baseline to 14 weeks
Reported as:
Least squares mean · pg/mL
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (VEGF(pg/mL))
pg/mLR500Placebo
Change From Baseline of Concentration of Inflammatory Biomarkers in Blood Serum: Primary Parameters of Interest (FAS) (VEGF(pg/mL))11.3 ± 12.80-21.5 ± 13.08
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.0728 · Mean difference (final values): 32.8 · 95% CI -3.0 to 168.6
SecondaryChange From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FEV1 (L))
Time frame:
Baseline to 16 weeks
Reported as:
Least squares mean · L
Change From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FEV1 (L))
LR500Placebo
Change From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FEV1 (L))0.028 ± 0.0212-0.035 ± 0.0212
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.0380 · Mean difference (final values): 0.063 · 95% CI 0.004 to 0.122
SecondaryChange From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FVC (L))
Time frame:
Baseline to 16 weeks
Reported as:
Least squares mean · L
Change From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FVC (L))
LR500Placebo
Change From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FVC (L))0.031 ± 0.0391-0.033 ± 0.391
Statistical analysis
  • R500 vs Placebo · ANCOVA · p = 0.2482 · Mean difference (final values): 0.064 · 95% CI -0.045 to 0.173
SecondaryWicoxon Signed-rank Test for Change From V2 to V6 in Post-bronchodilator FEV1/FVC

Wilcoxon test is a non-parametric test to evaluate differences among treatments in the variable that is being reported here. The data reported in the outcome measure data table are hodges Lehmann estimate of change from baseline in FEV1/FVC ratio.

Time frame:
Baseline to 16 weeks
Reported as:
Median · ratio
Wicoxon Signed-rank Test for Change From V2 to V6 in Post-bronchodilator FEV1/FVC
ratioR500Placebo
Wicoxon Signed-rank Test for Change From V2 to V6 in Post-bronchodilator FEV1/FVC0.5 (0 to 1)-0.5 (-1 to 0.5)
Statistical analysis
  • R500 vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.2629 · Median difference (final values): -1.00 · 95% CI -2.00 to 1.00Between treatment difference

Adverse events

Collected over 16 weeks. Non-serious events are listed at a 0.02% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
R500—8/79 (10.1%)69/79 (87.3%)
Placebo—5/79 (6.3%)57/79 (72.2%)
Most frequent serious events
Showing 10 of 14
Most frequent serious events
EventR500Placebo
COPDRespiratory, thoracic and mediastinal disorders3/791/79
HydroceleCongenital, familial and genetic disorders0/791/79
DyspepsiaGastrointestinal disorders1/790/79
Incarcerated herniaGeneral disorders0/791/79
DiverticulitisInfections and infestations1/790/79
PneumoniaInfections and infestations0/791/79
Influenza A virus test positiveInvestigations1/790/79
Synovial cystMusculoskeletal and connective tissue disorders1/790/79
Lung adenocarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/790/79
Rectal cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/790/79
Most frequent other events
Showing 10 of 37
Most frequent other events
EventR500Placebo
NasopharyngitisInfections and infestations13/7912/79
COPDRespiratory, thoracic and mediastinal disorders9/7912/79
CoughRespiratory, thoracic and mediastinal disorders10/7912/79
DiarrhoeaGastrointestinal disorders11/794/79
InsomniaPsychiatric disorders7/792/79
NauseaGastrointestinal disorders6/791/79
Weight decreasedInvestigations6/792/79
VomitingGastrointestinal disorders5/792/79
Back painMusculoskeletal and connective tissue disorders5/792/79
HaedacheNervous system disorders4/793/79

Baseline characteristics

Age, Continuous
Age, Continuous(Years)R500PlaceboTotal
Mean64 ± 8.2362.5 ± 8.4363.2 ± 8.34
Age, Customized
Age, Customized(Participants)R500PlaceboTotal
Between 18 and 65 years374683
>=65 years423375
Sex: Female, Male
Sex: Female, Male(Participants)R500PlaceboTotal
Female191837
Male6061121
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)R500PlaceboTotal
Asian011
Black or African American101
White7777154
Other112
Region of Enrollment
Region of Enrollment(Participants)R500PlaceboTotal
Europe7979158
08

Study locations

20 sites
  • København NV, DK-2400, Denmark
  • København NV, Denmark
  • Freiburg im Breisgau, Germany
  • Großhansdorf, Germany
  • Hanover, Germany
  • Heidelberg, Germany
  • Immenhausen, Germany
  • Kiel, Germany
  • Mainz, Germany
  • Bialystok, Poland
  • Krakow, Poland
  • Lodz, 90-153, Poland
  • Lodz, Poland
  • Lund, Sweden
  • Cottingham, United Kingdom
  • Dafen, United Kingdom
  • Leicester, United Kingdom
  • London, United Kingdom
  • Manchester, United Kingdom
  • Norwich, NR4 7UY, United Kingdom
09

References and documents

Publications

  • Rabe KF, Watz H, Baraldo S, Pedersen F, Biondini D, Bagul N, Hanauer G, Gohring UM, Purkayastha D, Roman J, Alagappan VKT, Saetta M. Anti-inflammatory effects of roflumilast in chronic obstructive pulmonary disease (ROBERT): a 16-week, randomised, placebo-controlled trial. Lancet Respir Med. 2018 Nov;6(11):827-836. doi: 10.1016/S2213-2600(18)30331-X. Epub 2018 Sep 14. PubMed 30224319 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 29, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01509677
Lead sponsor
AstraZeneca
Responsible party
Sponsor
First posted
Jan 13, 2012
Start date
Feb 1, 2012
Primary completion
Feb 1, 2016
Completion
Feb 1, 2016
Results posted
Nov 29, 2019
Last update
Nov 29, 2019

Study contacts

AstraZeneca AstraZeneca
study director · AstraZeneca

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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