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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-002905-31 | EudraCT Number | ||
| U1111-1137-4023 | Registry Identifier | WHO | |
| 11/SC/0494 | Registry Identifier | NRES |
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Company decision: No Safety or Efficacy Concerns
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Roflumilast | Active Comparator | added on to standard therapy for acute COPD exacerbations |
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| Placebo | Placebo Comparator | added on to standard therapy for acute COPD exacerbations |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Roflumilast | Drug | 500 µg tablet, od, oral administration in the morning after breakfast |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Initial Approach) | 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. | Baseline and Day 14 |
| Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Extended Approach) | 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. | Baseline and Day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Initial Approach) | 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. | Day 14 |
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Inclusion Criteria:
Main Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director Clinical Science | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Academic Unit of Respiratory Medicine, Royal Free Hospital, Jadwiga A. Wedzicha | London | NW3 2PF | United Kingdom | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28146642 | Derived | Mackay AJ, Patel ARC, Singh R, Sapsford RJ, Donaldson GC, Prasad N, Goehring UM, Nip TK, Wedzicha JA. Randomized Double-Blind Controlled Trial of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2017 Sep 1;196(5):656-659. doi: 10.1164/rccm.201612-2518LE. No abstract available. |
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Participants with a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) were enrolled equally in 1 of 2 treatment groups, once a day placebo or roflumilast 500 µg in Cycle 1. Participants were re-randomized in Cycle 2 to once a day placebo or roflumilast 500 µg and are counted as new participants.
Participants took part in the study at 1 investigative site in the United Kingdom from 16 February 2012 to 25 March 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | Roflumilast 500 μg | Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations. Eligible participants were re-randomized to receive either roflumilast 500 μg or placebo for 4 weeks in Cycle 2. |
| FG001 | Placebo | Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast added on to standard therapy for acute COPD exacerbations. Eligible participants were re-randomized to receive either roflumilast 500 μg or placebo for 4 weeks in Cycle 2. |
| FG002 | Roflumilast 500 µg (Cycle 2) | Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations in Cycle 2. |
| FG003 | Placebo (Cycle 2) | Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations in Cycle 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cycle 1 |
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| Cycle 2 |
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Full Analysis set consisted of all randomized patients who received at least 1 dose of investigational medicinal product (IMP)
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| ID | Title | Description |
|---|---|---|
| BG000 | Roflumilast 500 μg | Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | 10^6 cells/gram sputum | Baseline and Day 14 |
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Signing of informed consent until Follow-up Visit (Up to 56 days)
AEs were analyzed using an Initial Approach (all patients treated in Cycle 1) and an Extended Approach (all patients treated in Cycle 1 and patients re-randomized and treated in Cycle 2). The data from the 2 approaches are entered in one table. Please note: a result of 0 corresponds to no patients with AEs for the preferred term > the 5% threshold.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Roflumilast 500 μg (Initial Approach) | Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast added on to standard therapy for acute COPD exacerbations. Initial Approach Arm includes all participants who received treatment in Cycle 1. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director, Clinical Science | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| C424423 | Roflumilast |
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| Placebo |
| Drug |
tablet, od, oral administration in the morning after breakfast |
|
| Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Extended Approach) | 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. | Day 14 |
| Change From Baseline in Sputum Marker Total Cells (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Total Cells (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Percentage of Neutrophils (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Percentage of Macrophages (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Percentage of Macrophages (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Percentage of Eosinophils (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Percentage of Eosinophils (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Percentage of Lymphocyte (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Percentage of Lymphocytes (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Blood Biomarker Interleukin-1 Beta (IL-1β) (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Blood Biomarker IL-1β (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Blood Biomarker Fibrinogen (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Blood Biomarker Fibrinogen (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Blood Biomarker Glucose (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Blood Biomarker Glucose (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Forced Expiratory Volume (FEV1) (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Forced Expiratory Volume (FEV1) (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Forced Vital Capacity (FVC) (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in Forced Vital Capacity (FVC) (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in FEV1/FVC (Initial Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Change From Baseline in FEV1/FVC (Extended Approach) | 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. | Baseline and Day 7, Day 14, Day 28 and Day 56 |
| Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach) | 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). | Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
| Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach) | 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). | Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
| Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach) | 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. | 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) | 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. | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
| Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach) | 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. | Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
| Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach) | 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. | 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) | 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. | Baseline and 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) | 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. | 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) | 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. | 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) | 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. | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
| Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach) | 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. | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
| Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach) | 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. | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
| Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach) | 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. | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
| Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach) | 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. | 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) | 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. | 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) | 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. | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
| Exacerbation Length (Initial Approach) | 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. | 8 Weeks |
| Exacerbation Length (Extended Approach) | 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. | 8 Weeks |
| Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Initial Approach) | 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. | Baseline and Days 14 and 28 |
| Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Extended Approach) | 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. | Baseline and Days 14 and 28 |
| London |
| United Kingdom |
| Withdrawal by Subject |
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| COMPLETED |
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| NOT COMPLETED |
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Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
| BG002 | Total | Total of all reporting groups |
| participants |
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| Gender | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Smoking status | Number | participants |
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| Baseline COPD Assessment Test (CAT) Total Score | 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). | Number | participants |
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| Weight Category by Body Mass Index (BMI) | Number | participants |
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| Chronic Bronchitis | Number | participants |
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| Historical Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | Number | participants |
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| OG001 | Placebo | Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations. |
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| Primary | Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | 10^6 cells/gram sputum | Baseline and Day 14 |
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| Secondary | Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 14 |
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| Secondary | Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 14 |
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| Secondary | Change From Baseline in Sputum Marker Total Cells (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | 10^6 cells/gram sputum | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Total Cells (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | 10^6 cells/gram sputum | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | percentage of neutrophils | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Percentage of Neutrophils (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | percentage of neutrophils | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Percentage of Macrophages (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | percentage of macrophages | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Percentage of Macrophages (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | percentage of macrophages | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Percentage of Eosinophils (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | percentage of eosinophils | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Percentage of Eosinophils (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | percentage of macrophages | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Percentage of Lymphocyte (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | percentage of lymphocytes | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Percentage of Lymphocytes (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | percentage of lymphocytes | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | pg/mL | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | pg/mL | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | pg/mL | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | pg/mL | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | ng/mL | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | ng/mL | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | µg/mL | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | µg/mL | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | pg/mL | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | pg/mL | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Blood Biomarker Interleukin-1 Beta (IL-1β) (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | pg/mL | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Blood Biomarker IL-1β (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | pg/mL | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | mg/liter(L) | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | mg/L | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Blood Biomarker Fibrinogen (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | umol/L | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Blood Biomarker Fibrinogen (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | umol/L | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Blood Biomarker Glucose (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Blood Biomarker Glucose (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Forced Expiratory Volume (FEV1) (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | liters | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Forced Expiratory Volume (FEV1) (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | liters | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Forced Vital Capacity (FVC) (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | liters | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in Forced Vital Capacity (FVC) (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | liters | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in FEV1/FVC (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | percent | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Change From Baseline in FEV1/FVC (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | percent | Baseline and Day 7, Day 14, Day 28 and Day 56 |
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| Secondary | Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach) | 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). | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Mean | Standard Deviation | score on a scale | Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach) | 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). | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Mean | Standard Deviation | score on a scale | Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Mean | Standard Deviation | score on a scale | Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Mean | Standard Deviation | score on a scale | Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | liters/minute | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | liters/minute | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | hours | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | hours | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8 |
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| Secondary | Exacerbation Length (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Median | 95% Confidence Interval | days | 8 Weeks |
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| Secondary | Exacerbation Length (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Median | 95% Confidence Interval | days | 8 Weeks |
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| Secondary | Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Initial Approach) | 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. | Participants from the Intent-to-treat (ITT) population, all randomized participants, with data available at the given time-point. Initial Approach Analysis included all participants who received treatment in Cycle 1. | Posted | Least Squares Mean | Standard Error | meters/second | Baseline and Days 14 and 28 |
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| Secondary | Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Extended Approach) | 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. | Participants from the Intent-to-treat population, all randomized participants, with data available at the given time-point. Extended Approach Analysis included all participants who received treatment in Cycle 1 and participants who were re-randomized and received treatment in Cycle 2. | Posted | Least Squares Mean | Standard Error | meters/second | Baseline and Days 14 and 28 |
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| 4 |
| 38 |
| 35 |
| 38 |
| EG001 | Placebo (Initial Approach) | Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast added on to standard therapy for acute COPD exacerbations. Initial Approach Arm includes all participants who received treatment in Cycle 1. | 1 | 43 | 25 | 43 |
| EG002 | Roflumilast 500 µg (Extended Approach) | Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast added on to standard therapy for acute COPD exacerbations. Extended Approach Arm includes all participants who received treatment in Cycle 1 and those participants who were re-randomized and received treatment in Cycle 2. | 4 | 48 | 44 | 48 |
| EG003 | Placebo (Extended Approach) | Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast added on to standard therapy for acute COPD exacerbations. Extended Approach Arm includes all participants who received treatment in Cycle 1 and those participants who were re-randomized and received treatment in Cycle 2. | 1 | 47 | 28 | 47 |
| Pneumonia | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Supraventricular tachycardia | Cardiac disorders | MedDRA 17.0 | Systematic Assessment |
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| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 17.0 | Systematic Assessment |
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| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Oral candidiasis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Change at Day 28 (n=25, 37) |
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| Change at Day 56 (n=24, 33) |
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| Change at Day 28 (n=30, 40) |
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| Change at Day 56 (n=28, 36) |
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| Change at Day 28 (n=24, 34) |
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| Change at Day 56 (n=16, 30) |
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| Change at Day 28 (n=29, 36) |
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| Change at Day 56 (n=20, 32) |
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| Change at Day 28 (n=24, 34) |
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| Change at Day 56 (n=16, 30) |
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| Change at Day 28 (n=29, 36) |
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| Change at Day 56 (n=20, 32) |
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| Change at Day 28 (n=24, 34) |
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| Change at Day 56 (n=16, 30) |
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| Change at Day 28 (n=29, 36) |
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| Change at Day 56 (n=20, 32) |
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| Change at Day 28 (n=24, 34) |
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| Change at Day 56 (n=16, 30) |
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| Change at Day 28 (n=29, 36) |
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| Change at Day 56 (n=20, 32) |
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| Change at Day 28 (n=22, 35) |
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| Change at Day 56 (n=22, 29) |
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| Change at Day 28 (n=26, 38) |
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| Change at Day 56 (n=26, 32) |
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| Change at Day 28 (n=22, 35) |
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| Change at Day 56 (n=21, 29) |
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| Change at Day 28 (n=26, 38) |
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| Change at Day 56 (n=25, 32) |
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| Change at Day 28 (n=22, 35) |
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| Change at Day 56 (n=22, 29) |
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| Change at Day 28 (n=26, 38) |
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| Change at Day 56 (n=26, 32) |
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| Change at Day 28 (n=22, 35) |
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| Change at Day 56 (n=21, 30) |
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| Change at Day 28 (n=26, 38) |
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| Change at Day 56 (n=25, 33) |
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| Change at Day 28 (n=28, 40) |
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| Change at Day 56 (n=27, 40) |
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| Change at Day 28 (n=33, 44) |
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| Change at Day 56 (n=32, 44) |
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| Change at Day 28 (n=28, 40) |
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| Change at Day 56 (n=27, 40) |
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| Change at Day 28 (n=33, 44) |
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| Change at Day 56 (n=32, 44) |
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| Change at Day 28 (n=28, 38) |
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| Change at Day 56 (n=26, 40) |
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| Change at Day 28 (n=33, 42) |
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| Change at Day 56 (n=31, 44) |
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| Change at Day 28 (n=27, 36) |
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| Change at Day 56 (n=26, 38) |
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| Change at Day 28 (n=32, 40) |
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| Change at Day 56 (n=31, 42) |
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| Change at Day 28 (n=28, 40) |
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| Change at Day 56 (n=27, 40) |
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| Change at Day 28 (n=33, 44) |
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| Change at Day 56 (n=32, 43) |
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| Change at Day 28 (n=28, 40) |
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| Change at Day 56 (n=27, 40) |
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| Change at Day 28 (n=33, 44) |
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| Change at Day 56 (n=32, 44) |
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| Change at Day 28 (n=28, 40) |
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| Change at Day 56 (n=27, 40) |
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| Change at Day 28 (n=33, 44) |
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| Change at Day 56 (n=32, 44) |
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| Change at Day 28 (n=28, 40) |
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| Change at Day 56 (n=27, 40) |
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| Change at Day 28 (n=33, 44) |
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| Change at Day 56 (n=32, 44) |
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| Week 3 (n=24, 37) |
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| Week 4 (n=23, 38) |
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| Week 5 (n=21, 37) |
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| Week 6 (n=19, 37) |
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| Week 7 (n=20, 33) |
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| Week 8 (n=18, 30) |
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| Week 3 (n=29, 41) |
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| Week 4 (n=27, 42) |
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| Week 5 (n=25, 41) |
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| Week 6 (n=23, 41) |
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| Week 7 (n=24, 37) |
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| Week 8 (n=19, 30) |
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| Change at Week 3 (n=24, 37) |
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| Change at Week 4 (n=23, 38) |
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| Change at Week 5 (n=21, 37) |
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| Change at Week 6 (n=19, 37) |
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| Change at Week 7 (n=20, 33) |
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| Change at Week 8 (n=18, 30) |
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| Week 3 (n=29, 41) |
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| Week 4 (n=27, 42) |
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| Week 5 (n=25, 41) |
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| Week 6 (n=23, 41) |
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| Week 7 (n=24, 37) |
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| Week 8 (n=19, 30) |
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| Week 3 (n=24, 38) |
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| Week 4 (n=23, 38) |
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| Week 5 (n=21, 37) |
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| Week 6 (n=19, 37) |
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| Week 7 (n=20, 34) |
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| Week 8 (n=18, 32) |
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| Week 3 (n=29, 42) |
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| Week 4 (n=27, 42) |
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| Week 5 (n=25, 41) |
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| Week 6 (n=23, 41) |
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| Week 7 (n=24, 38) |
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| Week 8 (n=19, 33) |
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| Change at Week 3 (n=24, 38) |
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| Change at Week 4 (n=23, 38) |
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| Change at Week 5 (n=21, 37) |
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| Change at Week 6 (n=19, 37) |
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| Change at Week 7 (n=20, 34) |
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| Change at Week 8 (n=18, 32) |
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| Week 3 (n=29, 42) |
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| Week 4 (n=27, 42) |
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| Week 5 (n=25, 41) |
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| Week 6 (n=23, 41) |
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| Week 7 (n=24, 38) |
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| Week 8 9n=19, 33) |
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| Change at Week 3 (n=35, 40) |
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| Change at Week 4 (n=29, 39) |
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| Change at Week 5 (n=28, 38) |
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| Change at Week 6 (n=27, 37) |
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| Change at Week 7 (n=27, 36) |
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| Change at Week 8 (n=27, 35) |
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| Change at Week 3 (n=44, 44) |
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| Change at Week 4 (n=37, 43) |
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| Change at Week 5 (n=33, 42) |
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| Change at Week 6 (n=32, 41) |
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| Change at Week 7 (n=31, 40) |
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| Change at Week 8 (n=31, 39) |
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| Change at Week 3 (n=35, 42) |
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| Change at Week 4 (n=30, 40) |
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| Change at Week 5 (n=29, 39) |
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| Change at Week 6 (n=28, 39) |
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| Change at Week 7 (n=27, 37) |
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| Change at Week 8 (n=27, 36) |
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| Change at Week 3 (n=44, 46) |
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| Change at Week 4 (n=38, 44) |
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| Change at Week 5 (n=34, 43) |
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| Change at Week 6 (n=33, 43) |
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| Change at Week 7 (n=31, 41) |
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| Change at Week 8 (n=31, 40) |
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| Change at Week 3 (n=35, 42) |
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| Change at Week 4 (n=30, 40) |
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| Change at Week 5 (n=29, 39) |
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| Change at Week 6 (n=28, 39) |
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| Change at Week 7 (n=27, 37) |
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| Change at Week 8 (n=27, 36) |
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| Change at Week 3 (n=44, 46) |
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| Change at Week 4 (n=38, 44) |
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| Change at Week 5 (n=34, 43) |
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| Change at Week 6 (n=33, 43) |
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| Change at Week 7 (n=31, 41) |
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| Change at Week 8 (n=31, 40) |
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| Change at Week 3 (n=34, 40) |
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| Change at Week 4 (n=28, 39) |
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| Change at Week 5 (n=26, 38) |
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| Change at Week 6 (n=25, 35) |
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| Change at Week 7 (n=26, 35) |
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| Change at Week 8 (n=26, 34) |
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| Change at Week 3 (n=42, 44) |
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| Change at Week 4 (n=35, 43) |
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| Change at Week 5 (n=31, 42) |
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| Change at Week 6 (n=30, 39) |
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| Change at Week 7 (n=30, 39) |
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| Change at Week 8 (n=30, 38) |
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