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Clinical Trials/NCT01473758
NCT01473758TerminatedPhase 2

Effect of Roflumilast 500 μg Tablets Once Daily at Acute COPD Exacerbations Treated With Standard Therapy of Oral Steroids and Antibiotics. A Randomised, Double-blind, Placebo-controlled, Parallel-group Trial

AstraZeneca1 site in 1 country81 target enrollmentStarted: February 2012Last updated:
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Conditions
Interventions
Drugs

Trial Snapshot

Phase
Phase 2
Status
Terminated
Enrollment
81
Locations
1
Primary Endpoint
Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Extended Approach)
Study OverviewStudy DesignEligibility CriteriaArms & InterventionsOutcomesInvestigatorsSitesRecords & IdentifiersSimilar Trials

Study Overview

Brief Summary

The purpose of this trial is to investigate if roflumilast can reduce the neutrophilic inflammation at acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD). In addition, the potential benefit of roflumilast on severity and recovery periods of acute COPD exacerbations will be assessed using patient diaries and questionnaires.

Detailed Description

Participants will be asked whether they agree to participate in the measurements of arterial stiffness. Participants who agree will be included in the substudy, with the target of 60 patients with arterial stiffness measurements to complete the trial.

Study was terminated due to difficulty in identifying further eligible patients for this exploratory study within a reasonable time.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Eligibility Criteria

Ages
40 Years to — (Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • •Written informed consent (IC)
  • •Age ≥ 40 years
  • •History of COPD for at least 12 months prior to enrollment (Visit V0)
  • •Chronic productive cough for 3 months in each of the 2 years prior to enrollment (if other causes of productive cough have been excluded) and/or an exacerbation with predominantly bronchitic symptoms at enrollment
  • •Presentation of an acute exacerbation of COPD that will be associated with increased sputum volume or change in sputum colour
  • •Documented fixed airway obstruction determined by an FEV1/FVC ratio (post-bronchodilator) < 70% (if a pulmonary function test is not possible at Visit V0 a previous measurement can be taken which must not be older than 6 months)
  • •Former smoker (defined as: smoking cessation at least 1 year ago) or current smoker both with a smoking history of at least 10 pack years

Exclusion Criteria

  • •Diagnosis of asthma and/or other relevant lung disease
  • •Known alpha-1-antitrypsin deficiency
  • •Recurrent exacerbations (within 8 weeks of a preceding exacerbation)
  • •Treatment of current exacerbation with oral corticosteroids and/or antibiotics already started at enrollment
  • •Treatment with PDE4 inhibitors within 3 months prior to Visit V0
  • •Other protocol-defined exclusion criteria may apply

Arms & Interventions

Roflumilast

Active Comparator

added on to standard therapy for acute COPD exacerbations

Intervention: Roflumilast (Drug)

Placebo

Placebo Comparator

added on to standard therapy for acute COPD exacerbations

Intervention: Placebo (Drug)

Outcomes

Primary Outcomes

Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Extended Approach)

Time Frame: Baseline and Day 14

Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used with neutrophil count at Baseline and treatment as independent variables, fixed effects.

Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Initial Approach)

Time Frame: Baseline and Day 14

Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used with neutrophil count at Baseline and treatment as independent variables, fixed effects.

Secondary Outcomes

  • Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Initial Approach)(Day 14)
  • Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Extended Approach)(Day 14)
  • Change From Baseline in Sputum Marker Percentage of Macrophages (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Total Cells (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Percentage of Neutrophils (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Percentage of Eosinophils (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Percentage of Lymphocyte (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Blood Biomarker IL-1β (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Forced Expiratory Volume (FEV1) (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Total Cells (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Percentage of Macrophages (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Percentage of Eosinophils (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Percentage of Lymphocytes (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Blood Biomarker Interleukin-1 Beta (IL-1β) (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Blood Biomarker Fibrinogen (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Blood Biomarker Fibrinogen (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Blood Biomarker Glucose (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Blood Biomarker Glucose (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Forced Expiratory Volume (FEV1) (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in FEV1/FVC (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)(Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Change From Baseline in Forced Vital Capacity (FVC) (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in Forced Vital Capacity (FVC) (Extended Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Baseline in FEV1/FVC (Initial Approach)(Baseline and Day 7, Day 14, Day 28 and Day 56)
  • Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)(Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)(Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)(Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)(Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)(Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)(Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)(Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach)(Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach)(Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach)(Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach)(Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach)(Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach)(Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach)(Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach)(Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8)
  • Exacerbation Length (Initial Approach)(8 Weeks)
  • Exacerbation Length (Extended Approach)(8 Weeks)
  • Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Extended Approach)(Baseline and Days 14 and 28)
  • Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Initial Approach)(Baseline and Days 14 and 28)

Investigators

Sponsor Class
Industry
Responsible Party
Sponsor

Study Sites (1)

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