- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01509677
Trial to Assess the Anti-inflammatory Effects of Roflumilast in Chronic Obstructive Pulmonary Disease
A 16-week, Randomized, Placebo-controlled, Double Blind, and Parallel Group Trial to Assess the Anti-inflammatory Effects of Roflumilast in Chronic Obstructive Pulmonary Disease
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Kobenhavn NV, Denmark
-
København NV, Denmark, DK-2400
-
-
-
-
-
Freiburg, Germany
-
Grosshansdorf, Germany
-
Hannover, Germany
-
Heidelberg, Germany
-
Immenhausen, Germany
-
Kiel, Germany
-
Mainz, Germany
-
-
-
-
-
Bialystok, Poland
-
Krakow, Poland
-
Lodz, Poland, 90-153
-
Lodz, Poland
-
-
-
-
-
Lund, Sweden
-
-
-
-
-
Cottingham, United Kingdom
-
Dafen, United Kingdom
-
Leicester, United Kingdom
-
London, United Kingdom
-
Manchester, United Kingdom
-
Norwich, United Kingdom, NR4 7UY
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Roflumilast
500 μg tablet, once daily, oral administration in the morning after breakfast
|
500 μg tablet, once daily, oral administration in the morning after breakfast
Other Names:
|
Placebo Comparator: Placebo
tablet, once daily, oral administration in the morning after breakfast
|
tablet, once daily, oral administration in the morning after breakfast
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue.
Time Frame: 16 weeks
|
16 weeks
|
Change in Number of CD8+ Inflammatory Cells in Bronchial Biopsy Tissue
Time Frame: Baseline to 16 weeks
|
Baseline to 16 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
CD68+ Count in Biopsied Material (Submucosa)
Time Frame: 16 weeks
|
16 weeks
|
|
CD68+ Cell Count in Biopsied Material (Submucosa): Poisson Regression (Ratio)
Time Frame: 16 weeks
|
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.
|
16 weeks
|
Change From V2 to V6 in CD68+ Cell Count (Cells/mm^2) in Biopsied Material (Submucosa) (ITT)
Time Frame: Baseline and 16 weeks
|
Baseline and 16 weeks
|
|
CD4+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model
Time Frame: 16 weeks
|
CD4+ Cell Counts in biopsied Material (submucosa):poisson regression model.
Clarification: Measure type "Number" refers to "Risk of each treatment group".
|
16 weeks
|
CD45+ Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model
Time Frame: 16 weeks
|
CD45+ Cell Counts in biopsied Material (submucosa):poisson regression model.
Clarification: Measure type "Number" refers to "treatment risk"
|
16 weeks
|
Neutrophils Cell Counts in Biopsied Material (Submucosa):Poisson Regression Model
Time Frame: Baseline to 14 weeks
|
Neutrophils Cell Counts in biopsied Material (submucosa):poisson regression model.
Clarification: Measure type "Number" refers to "Treatment risk"
|
Baseline to 14 weeks
|
CD8+ Cell Count in Biopsied Material (Bronchial Epithelium): Poisson Regression Model
Time Frame: 16 weeks
|
CD8+ Cell Count in biopsied material (Bronchial Epithelium): poisson regression model.
Clarification: Measure Type "Number" refers to "Treatment risk"
|
16 weeks
|
CD68+ Cell Count in Biopsied Material (Bronchial Epithelium):Poisson Regression Model
Time Frame: 16 weeks
|
CD68+ Cell Count in biopsied material (Bronchial Epithelium):poisson regression model.
Clarification: Measure type "Number" refers to "Treatment Risk"
|
16 weeks
|
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
|
Baseline to 14 weeks
|
|
Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Macrophages/mL): Between-Treatment Difference
Time Frame: Baseline to 14 weeks
|
Baseline to 14 weeks
|
|
Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Eosinophils/mL): Between-Treatment Difference
Time Frame: Baseline to 14 weeks
|
Baseline to 14 weeks
|
|
Change From V1 to V5 in Absolute Cell Count inInduced Sputum (10^6 Lymphocytes/mL): Between-Treatment Difference
Time Frame: BAseline to 14 weeks
|
BAseline to 14 weeks
|
|
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Neutrophils/mL)
Time Frame: Baseline to 14 weeks
|
Baseline to 14 weeks
|
|
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Macrophages/mL)
Time Frame: Baseline to 14 weeks
|
Baseline to 14 weeks
|
|
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Eosinophils/mL)
Time Frame: Baseline to 14 weeks
|
Baseline to 14 weeks
|
|
Change From V1 to V5 in Differential Cell Count in Induced Sputum(10^6 Lymphocytes)/mL)
Time Frame: Baseline to 14 weeks
|
Baseline to 14 weeks
|
|
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
|
Baseline to 14 weeks
|
|
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
|
Baseline to 14 weeks
|
|
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
|
Baseline to 14 weeks
|
|
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
|
Baseline to 14 weeks
|
|
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
|
Baseline to 14 weeks
|
|
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
|
Baseline to 14 weeks
|
|
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
|
Baseline to 14 weeks
|
|
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
|
Baseline to 14 weeks
|
|
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
|
Baseline to 14 weeks
|
|
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
|
Baseline to 14 weeks
|
|
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
|
Baseline to 14 weeks
|
|
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
|
Baseline to 14 weeks
|
|
Change From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FEV1 (L))
Time Frame: Baseline to 16 weeks
|
Baseline to 16 weeks
|
|
Change From Baseline in Lung Function Variables: Between-Treatment Differences (FAS) (FVC (L))
Time Frame: Baseline to 16 weeks
|
Baseline to 16 weeks
|
|
Wicoxon Signed-rank Test for Change From V2 to V6 in Post-bronchodilator FEV1/FVC
Time Frame: Baseline to 16 weeks
|
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.
|
Baseline to 16 weeks
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- RO-2455-402-RD
- 2011-000582-13 (EudraCT Number)
- U1111-1155-8767 (Registry Identifier: WHO)
- D7120C00003 (Other Identifier: Sponsor Identifier)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Obstructive Pulmonary Disease
-
Spire, Inc.ResMedCompletedSevere Chronic Obstructive Pulmonary Disease | Moderate Chronic Obstructive Pulmonary DiseaseUnited States
-
Karaganda Medical UniversityCompletedChronic Obstructive Pulmonary Disease | Chronic Obstructive Pulmonary Disease Moderate | Chronic Obstructive Pulmonary Disease SevereKazakhstan
-
Randall DebattistaUniversity of Malta, Faculty of Health SciencesNot yet recruitingChronic Obstructive Pulmonary Disease Moderate | Acute Exacerbation of COPD | Chronic Obstructive Pulmonary Disease Severe
-
Cukurova UniversityCompletedAnesthesia | Chronic Obstructive Pulmonary Disease Moderate | Lungcancer | Chronic Obstructive Pulmonary Disease Severe | Chronic Obstructive Pulmonary Disease MildTurkey
-
National Taipei University of Nursing and Health...TerminatedChronic Pulmonary Disease | Chronic Obstructive Pulmonary Disease Exacerbation | Chronic Obstructive Pulmonary Disease With ExacerbationTaiwan
-
Taipei Medical UniversityUnknownChronic Obstructive Pulmonary Disease Severe | Chronic Obstructive Pulmonary Disease End StageTaiwan
-
Kırıkkale UniversityRecruitingCOPD (Chronic Obstructive Pulmonary Disease)Turkey
-
Hopital FochAir Liquide SARecruitingChronic Obstructive Pulmonary Disease SevereFrance
-
Fundación para la Investigación del Hospital Clínico...Not yet recruitingCOPD, Chronic Obstructive Pulmonary DiseaseSpain
-
Canandaigua VA Medical CenterRecruitingChronic Obstructive Pulmonary Disease ModerateUnited States
Clinical Trials on Roflumilast
-
University of MiamiForest LaboratoriesCompleted
-
Rao DermatologyRecruitingHealthy SkinUnited States
-
Asan Medical CenterUnknownChronic Obstructive Pulmonary DiseaseKorea, Republic of
-
Arcutis Biotherapeutics, Inc.CompletedAtopic Dermatitis EczemaUnited States, Canada
-
FLUIDDA nvTerminatedPulmonary Disease, Chronic ObstructiveBelgium
-
AstraZenecaCompletedCOPDSweden, Germany, United States, Norway
-
AstraZenecaCompletedAsthmaUnited States, Russian Federation, Ukraine
-
AstraZenecaCompletedChronic Obstructive Pulmonary DiseaseChina
-
AstraZenecaCompleted
-
AstraZenecaCompletedChronic Obstructive Pulmonary Disease | COPDUnited States, France, Poland, South Africa, Canada, Germany