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Effect of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease (TREAT)

This study has been terminated.
(Company decision: No Safety or Efficacy Concerns)
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01473758
First received: October 31, 2011
Last updated: August 31, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Chronic Obstructive Pulmonary Disease With (Acute) Exacerbation
Drug: Roflumilast
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Initial Approach) [ Time Frame: Baseline and Day 14 ] [ Designated as safety issue: No ]
    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 (Extended Approach) [ Time Frame: Baseline and Day 14 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Initial Approach) [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    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) and were determined with a Neubauer hemocytometer.

  • Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Extended Approach) [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    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) and were determined with a Neubauer hemocytometer.

  • Change From Baseline in Sputum Marker Total Cells (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    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. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Total Cells (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    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. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of neutrophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Percentage of Neutrophils (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of neutrophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction. A negative change from Baseline indicates improvement.

  • Change From Baseline in Sputum Marker Percentage of Macrophages (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of macrophages was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Percentage of Macrophages (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of macrophages was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Percentage of Eosinophils (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of eosinophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Percentage of Eosinophils (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of eosinophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Percentage of Lymphocyte (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of lymphocytes was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Percentage of Lymphocytes (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of lymphocytes was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-6 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-6 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-8 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-8 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker MPO was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker MPO was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker Neutrophil Elastase was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker Neutrophil Elastase was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Blood was collected and serum biomarker IL-6 was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Blood was collected and serum biomarker IL-6 was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Blood Biomarker Interleukin-1 Beta (IL-1β) (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Blood was collected and serum biomarker IL-1β was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Blood Biomarker IL-1β (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Blood was collected and serum biomarker IL-1β was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Blood was collected and serum biomarker CRP was measured using Roche Modular Analytics E 170 Module. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Blood was collected and serum biomarker CRP was measured using Roche Modular Analytics E 170 Module. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Blood Biomarker Fibrinogen (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Biomarker Plasma fibrinogen was determined using the method described by Clauss. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Blood Biomarker Fibrinogen (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Biomarker Plasma fibrinogen was determined using the method described by Clauss. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Blood Biomarker Glucose (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Blood was collected and analyzed for serum glucose levels. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Blood Biomarker Glucose (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Blood was collected and analyzed for serum glucose levels. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Forced Expiratory Volume (FEV1) (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.

  • Change From Baseline in Forced Expiratory Volume (FEV1) (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.

  • Change From Baseline in Forced Vital Capacity (FVC) (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Forced vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.

  • Change From Baseline in Forced Vital Capacity (FVC) (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    Forced vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.

  • Change From Baseline in FEV1/FVC (Initial Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    FEV1/FVC is the percentage of the vital capacity which is expired in the first second of maximal expiration. In healthy patients the FEV1/FVC is usually around 70%. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.

  • Change From Baseline in FEV1/FVC (Extended Approach) [ Time Frame: Baseline and Day 7, Day 14, Day 28 and Day 56 ] [ Designated as safety issue: No ]
    FEV1/FVC is the percentage of the vital capacity which is expired in the first second of maximal expiration. In healthy patients the FEV1/FVC is usually around 70%. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.

  • Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach) [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst).

  • Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach) [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst).

  • Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach) [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst). A negative change from Baseline indicates improvement. Covariates for MMRM are stable state value, treatment, time point, and treatment by time point interaction.

  • Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach) [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst). A negative change from Baseline indicates improvement. Covariates for MMRM are stable state value, treatment, time point, and treatment by time point interaction.

  • Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach) [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status.

  • Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach) [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status.

  • Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach) [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, time point, treatment by time point and baseline by time point interaction.

  • Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach) [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, time point, treatment by time point and baseline by time point interaction.

  • Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach) [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    Morning post-medication PEF (the best of 3 attempts measured with a mini-Wright peak-flow meter) was recorded in a daily diary. A positive change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.

  • Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach) [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    Morning post-medication PEF (the best of 3 attempts measured with a mini-Wright peak-flow meter) was recorded in a daily diary. A positive change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.

  • Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach) [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    Any increase in the following respiratory symptoms: dyspnea, sputum purulence, sputum amount, wheeze, sore throat, cough, fever, symptoms of a common cold, ie, nasal congestion and discharge over the previous 24 hours were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.

  • Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach) [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    Any increase in the following respiratory symptoms: dyspnea, sputum purulence, sputum amount, wheeze, sore throat, cough, fever, symptoms of a common cold, ie, nasal congestion and discharge over the previous 24 hours were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.

  • Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach) [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    Any changes in the participant's usual treatment were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.

  • Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach) [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    Any changes in the participant's usual treatment were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.

  • Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach) [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    Estimates of the length of time the participants were out of their own home on the previous day were recorded in a daily diary. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.

  • Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach) [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 ] [ Designated as safety issue: No ]
    Estimates of the length of time the participants were out of their own home on the previous day were recorded in a daily diary. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.

  • Exacerbation Length (Initial Approach) [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
    Exacerbation length is the period from start of increased symptoms to end of increased symptoms; the last day of an exacerbation was to be followed by 2 days without symptom entries in the diary.

  • Exacerbation Length (Extended Approach) [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
    Exacerbation length is the period from start of increased symptoms to end of increased symptoms; the last day of an exacerbation was to be followed by 2 days without symptom entries in the diary.

  • Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Initial Approach) [ Time Frame: Baseline and Days 14 and 28 ] [ Designated as safety issue: No ]
    Carotid-femoral aortic pulse wave velocity (aPWV) will be measured in a subset of participants to determine changes in arterial stiffness. A negative change from Baseline indicates improvement. Covariates for MMRM are baseline value, treatment, visit, and treatment by visit interaction.

  • Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Extended Approach) [ Time Frame: Baseline and Days 14 and 28 ] [ Designated as safety issue: No ]
    Carotid-femoral aortic pulse wave velocity (aPWV) will be measured in a subset of participants to determine changes in arterial stiffness. A negative change from Baseline indicates improvement. Covariates for MMRM are baseline value, treatment, visit, and treatment by visit interaction.


Enrollment: 81
Study Start Date: February 2012
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Roflumilast
added on to standard therapy for acute COPD exacerbations
Drug: Roflumilast
500 µg tablet, od, oral administration in the morning after breakfast
Placebo Comparator: Placebo
added on to standard therapy for acute COPD exacerbations
Drug: Placebo
tablet, od, oral administration in the morning after breakfast

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.

  Eligibility

Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

Main 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01473758

Locations
United Kingdom
Academic Unit of Respiratory Medicine, Royal Free Hospital, Jadwiga A. Wedzicha
London, United Kingdom, NW3 2PF
London, United Kingdom
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Clinical Science Takeda
  More Information

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01473758     History of Changes
Other Study ID Numbers: RO-2455-405-RD  2011-002905-31  U1111-1137-4023  11/SC/0494 
Study First Received: October 31, 2011
Results First Received: July 23, 2015
Last Updated: August 31, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Takeda:
COPD
Chronic obstructive pulmonary disease
Roflumilast

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on December 09, 2016