Trial Outcomes & Findings for Effect of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease (NCT NCT01473758)
NCT ID: NCT01473758
Last Updated: 2017-02-14
Results Overview
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.
TERMINATED
PHASE2
81 participants
Baseline and Day 14
2017-02-14
Participant Flow
Participants took part in the study at 1 investigative site in the United Kingdom from 16 February 2012 to 25 March 2014.
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.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Cycle 1
STARTED
|
38
|
43
|
0
|
0
|
|
Cycle 1
COMPLETED
|
27
|
40
|
0
|
0
|
|
Cycle 1
NOT COMPLETED
|
11
|
3
|
0
|
0
|
|
Cycle 2
STARTED
|
0
|
0
|
10
|
4
|
|
Cycle 2
COMPLETED
|
0
|
0
|
5
|
4
|
|
Cycle 2
NOT COMPLETED
|
0
|
0
|
5
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Cycle 1
Adverse Event
|
10
|
2
|
0
|
0
|
|
Cycle 1
Withdrawal by Subject
|
1
|
1
|
0
|
0
|
|
Cycle 2
Adverse Event
|
0
|
0
|
5
|
0
|
Baseline Characteristics
Effect of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Baseline characteristics by cohort
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Total
n=81 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Chronic Bronchitis
No
|
14 participants
n=5 Participants
|
17 participants
n=7 Participants
|
31 participants
n=5 Participants
|
|
Chronic Bronchitis
Yes
|
24 participants
n=5 Participants
|
26 participants
n=7 Participants
|
50 participants
n=5 Participants
|
|
Historical Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
< 2
|
28 participants
n=5 Participants
|
28 participants
n=7 Participants
|
56 participants
n=5 Participants
|
|
Historical Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
≥ 2
|
10 participants
n=5 Participants
|
15 participants
n=7 Participants
|
25 participants
n=5 Participants
|
|
Age, Customized
≤ 65 years
|
7 participants
n=5 Participants
|
11 participants
n=7 Participants
|
18 participants
n=5 Participants
|
|
Age, Customized
> 65 years
|
31 participants
n=5 Participants
|
32 participants
n=7 Participants
|
63 participants
n=5 Participants
|
|
Gender
Female
|
16 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Gender
Male
|
22 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
36 participants
n=5 Participants
|
42 participants
n=7 Participants
|
78 participants
n=5 Participants
|
|
Smoking status
Non-smoker
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Smoking status
Current smoker
|
8 participants
n=5 Participants
|
11 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Smoking status
Former smoker
|
30 participants
n=5 Participants
|
32 participants
n=7 Participants
|
62 participants
n=5 Participants
|
|
Baseline COPD Assessment Test (CAT) Total Score
< 10
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Baseline COPD Assessment Test (CAT) Total Score
≥ 10
|
16 participants
n=5 Participants
|
25 participants
n=7 Participants
|
41 participants
n=5 Participants
|
|
Baseline COPD Assessment Test (CAT) Total Score
Missing
|
20 participants
n=5 Participants
|
15 participants
n=7 Participants
|
35 participants
n=5 Participants
|
|
Weight Category by Body Mass Index (BMI)
Underweight
|
3 participants
n=5 Participants
|
0 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Weight Category by Body Mass Index (BMI)
Normal Weight
|
15 participants
n=5 Participants
|
18 participants
n=7 Participants
|
33 participants
n=5 Participants
|
|
Weight Category by Body Mass Index (BMI)
Overweight
|
11 participants
n=5 Participants
|
15 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Weight Category by Body Mass Index (BMI)
Obese
|
9 participants
n=5 Participants
|
9 participants
n=7 Participants
|
18 participants
n=5 Participants
|
|
Weight Category by Body Mass Index (BMI)
Missing
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 14Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=29 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=37 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Initial Approach)
|
-18.705 10^6 cells/gram sputum
Standard Error 2.263
|
-20.109 10^6 cells/gram sputum
Standard Error 1.995
|
PRIMARY outcome
Timeframe: Baseline and Day 14Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=37 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=39 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Extended Approach)
|
-19.569 10^6 cells/gram sputum
Standard Error 1.906
|
-19.157 10^6 cells/gram sputum
Standard Error 1.855
|
SECONDARY outcome
Timeframe: Day 14Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=16 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=29 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Initial Approach)
|
37.5 percentage of participants
Interval 15.2 to 64.6
|
55.2 percentage of participants
Interval 35.7 to 73.6
|
SECONDARY outcome
Timeframe: Day 14Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=20 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=31 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Extended Approach)
|
45.0 percentage of participants
Interval 23.1 to 68.5
|
51.6 percentage of participants
Interval 33.1 to 69.8
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Total Cells (Initial Approach)
Change at Day 7 (n=35, 39)
|
-25.559 10^6 cells/gram sputum
Standard Error 3.529
|
-27.563 10^6 cells/gram sputum
Standard Error 3.334
|
|
Change From Baseline in Sputum Marker Total Cells (Initial Approach)
Change at Day 14 (n=32, 38)
|
-21.813 10^6 cells/gram sputum
Standard Error 2.706
|
-25.111 10^6 cells/gram sputum
Standard Error 2.505
|
|
Change From Baseline in Sputum Marker Total Cells (Initial Approach)
Change at Day 28 (n=25, 37)
|
-29.200 10^6 cells/gram sputum
Standard Error 4.022
|
-22.218 10^6 cells/gram sputum
Standard Error 3.362
|
|
Change From Baseline in Sputum Marker Total Cells (Initial Approach)
Change at Day 56 (n=24, 33)
|
-24.477 10^6 cells/gram sputum
Standard Error 2.708
|
-26.474 10^6 cells/gram sputum
Standard Error 2.341
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=48 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=46 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Total Cells (Extended Approach)
Change at Day 14 (n=41, 42)
|
-23.512 10^6 cells/gram sputum
Standard Error 2.448
|
-25.332 10^6 cells/gram sputum
Standard Error 2.471
|
|
Change From Baseline in Sputum Marker Total Cells (Extended Approach)
Change at Day 7 (n=45, 43)
|
-26.634 10^6 cells/gram sputum
Standard Error 3.030
|
-26.335 10^6 cells/gram sputum
Standard Error 3.124
|
|
Change From Baseline in Sputum Marker Total Cells (Extended Approach)
Change at Day 28 (n=30, 40)
|
-29.023 10^6 cells/gram sputum
Standard Error 3.347
|
-22.920 10^6 cells/gram sputum
Standard Error 2.947
|
|
Change From Baseline in Sputum Marker Total Cells (Extended Approach)
Change at Day 56 (n=28, 36)
|
-19.551 10^6 cells/gram sputum
Standard Error 3.920
|
-26.855 10^6 cells/gram sputum
Standard Error 3.536
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=36 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach)
Change at Day 7 (n=30, 35)
|
-11.325 percentage of neutrophils
Standard Error 3.837
|
-14.484 percentage of neutrophils
Standard Error 3.559
|
|
Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach)
Change at Day 14 (n=31, 37)
|
-16.770 percentage of neutrophils
Standard Error 3.983
|
-20.346 percentage of neutrophils
Standard Error 3.550
|
|
Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach)
Change at Day 28 (n=24, 34)
|
-27.760 percentage of neutrophils
Standard Error 5.275
|
-13.837 percentage of neutrophils
Standard Error 4.498
|
|
Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach)
Change at Day 56 (n=16, 30)
|
-19.663 percentage of neutrophils
Standard Error 5.561
|
-17.047 percentage of neutrophils
Standard Error 4.229
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=46 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=46 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Percentage of Neutrophils (Extended Approach)
Change at Day 7 (n=37, 39)
|
-14.637 percentage of neutrophils
Standard Error 3.748
|
-16.060 percentage of neutrophils
Standard Error 3.713
|
|
Change From Baseline in Sputum Marker Percentage of Neutrophils (Extended Approach)
Change at Day 14 (n=39, 40)
|
-20.690 percentage of neutrophils
Standard Error 3.758
|
-21.052 percentage of neutrophils
Standard Error 3.678
|
|
Change From Baseline in Sputum Marker Percentage of Neutrophils (Extended Approach)
Change at Day 28 (n=29, 36)
|
-29.848 percentage of neutrophils
Standard Error 4.721
|
-14.664 percentage of neutrophils
Standard Error 4.371
|
|
Change From Baseline in Sputum Marker Percentage of Neutrophils (Extended Approach)
Change at Day 56 (n=20, 32)
|
-21.327 percentage of neutrophils
Standard Error 5.009
|
-17.328 percentage of neutrophils
Standard Error 4.188
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=36 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Percentage of Macrophages (Initial Approach)
Change at Day 7 (n=30, 35)
|
11.393 percentage of macrophages
Standard Error 3.837
|
15.430 percentage of macrophages
Standard Error 3.559
|
|
Change From Baseline in Sputum Marker Percentage of Macrophages (Initial Approach)
Change at Day 14 (n=31, 37)
|
16.062 percentage of macrophages
Standard Error 3.929
|
20.774 percentage of macrophages
Standard Error 3.506
|
|
Change From Baseline in Sputum Marker Percentage of Macrophages (Initial Approach)
Change at Day 28 (n=24, 34)
|
27.535 percentage of macrophages
Standard Error 5.284
|
13.382 percentage of macrophages
Standard Error 4.503
|
|
Change From Baseline in Sputum Marker Percentage of Macrophages (Initial Approach)
Change at Day 56 (n=16, 30)
|
16.593 percentage of macrophages
Standard Error 5.539
|
15.877 percentage of macrophages
Standard Error 4.171
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=46 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=46 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Percentage of Macrophages (Extended Approach)
Change at Day 7 (n=37, 39)
|
14.679 percentage of macrophages
Standard Error 3.740
|
17.228 percentage of macrophages
Standard Error 3.704
|
|
Change From Baseline in Sputum Marker Percentage of Macrophages (Extended Approach)
Change at Day 14 (n=39, 40)
|
20.331 percentage of macrophages
Standard Error 3.745
|
21.599 percentage of macrophages
Standard Error 3.667
|
|
Change From Baseline in Sputum Marker Percentage of Macrophages (Extended Approach)
Change at Day 28 (n=29, 36)
|
29.510 percentage of macrophages
Standard Error 4.717
|
14.463 percentage of macrophages
Standard Error 4.367
|
|
Change From Baseline in Sputum Marker Percentage of Macrophages (Extended Approach)
Change at Day 56 (n=20, 32)
|
19.075 percentage of macrophages
Standard Error 5.003
|
16.322 percentage of macrophages
Standard Error 4.156
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=36 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Percentage of Eosinophils (Initial Approach)
Change at Day 7 (n=30, 35)
|
-0.259 percentage of eosinophils
Standard Error 0.245
|
-0.100 percentage of eosinophils
Standard Error 0.225
|
|
Change From Baseline in Sputum Marker Percentage of Eosinophils (Initial Approach)
Change at Day 14 (n=31, 37)
|
-0.110 percentage of eosinophils
Standard Error 0.326
|
-0.188 percentage of eosinophils
Standard Error 0.288
|
|
Change From Baseline in Sputum Marker Percentage of Eosinophils (Initial Approach)
Change at Day 28 (n=24, 34)
|
0.043 percentage of eosinophils
Standard Error 1.209
|
1.597 percentage of eosinophils
Standard Error 1.020
|
|
Change From Baseline in Sputum Marker Percentage of Eosinophils (Initial Approach)
Change at Day 56 (n=16, 30)
|
2.187 percentage of eosinophils
Standard Error 2.278
|
1.086 percentage of eosinophils
Standard Error 1.766
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=46 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=46 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Percentage of Eosinophils (Extended Approach)
Change at Day 7 (n=37, 39)
|
-0.341 percentage of macrophages
Standard Error 0.206
|
-0.141 percentage of macrophages
Standard Error 0.202
|
|
Change From Baseline in Sputum Marker Percentage of Eosinophils (Extended Approach)
Change at Day 14 (n=39, 40)
|
-0.174 percentage of macrophages
Standard Error 0.271
|
-0.214 percentage of macrophages
Standard Error 0.263
|
|
Change From Baseline in Sputum Marker Percentage of Eosinophils (Extended Approach)
Change at Day 28 (n=29, 36)
|
0.031 percentage of macrophages
Standard Error 1.044
|
1.518 percentage of macrophages
Standard Error 0.952
|
|
Change From Baseline in Sputum Marker Percentage of Eosinophils (Extended Approach)
Change at Day 56 (n=20, 32)
|
1.714 percentage of macrophages
Standard Error 1.969
|
0.913 percentage of macrophages
Standard Error 1.655
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=36 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Percentage of Lymphocyte (Initial Approach)
Change at Day 28 (n=24, 34)
|
0.039 percentage of lymphocytes
Standard Error 0.183
|
-0.325 percentage of lymphocytes
Standard Error 0.155
|
|
Change From Baseline in Sputum Marker Percentage of Lymphocyte (Initial Approach)
Change at Day 7 (n=30, 35)
|
0.229 percentage of lymphocytes
Standard Error 0.353
|
0.182 percentage of lymphocytes
Standard Error 0.326
|
|
Change From Baseline in Sputum Marker Percentage of Lymphocyte (Initial Approach)
Change at Day 14 (n=31, 37)
|
0.430 percentage of lymphocytes
Standard Error 0.254
|
0.295 percentage of lymphocytes
Standard Error 0.225
|
|
Change From Baseline in Sputum Marker Percentage of Lymphocyte (Initial Approach)
Change at Day 56 (n=16, 30)
|
-0.095 percentage of lymphocytes
Standard Error 0.187
|
-0.051 percentage of lymphocytes
Standard Error 0.137
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=46 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=46 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Percentage of Lymphocytes (Extended Approach)
Change at Day 7 (n=37, 39)
|
0.109 percentage of lymphocytes
Standard Error 0.308
|
-0.015 percentage of lymphocytes
Standard Error 0.303
|
|
Change From Baseline in Sputum Marker Percentage of Lymphocytes (Extended Approach)
Change at Day 14 (n=39, 40)
|
0.309 percentage of lymphocytes
Standard Error 0.250
|
0.195 percentage of lymphocytes
Standard Error 0.243
|
|
Change From Baseline in Sputum Marker Percentage of Lymphocytes (Extended Approach)
Change at Day 28 (n=29, 36)
|
-0.118 percentage of lymphocytes
Standard Error 0.173
|
-0.431 percentage of lymphocytes
Standard Error 0.158
|
|
Change From Baseline in Sputum Marker Percentage of Lymphocytes (Extended Approach)
Change at Day 56 (n=20, 32)
|
-0.203 percentage of lymphocytes
Standard Error 0.164
|
-0.208 percentage of lymphocytes
Standard Error 0.132
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=36 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=42 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Initial Approach)
Change at Day 7 (n=31, 38)
|
-1317.400 pg/mL
Standard Error 143.748
|
-934.624 pg/mL
Standard Error 133.217
|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Initial Approach)
Change at Day 14 (n=30, 35)
|
-822.715 pg/mL
Standard Error 221.328
|
-695.955 pg/mL
Standard Error 206.201
|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Initial Approach)
Change at Day 28 (n=22, 35)
|
-1232.929 pg/mL
Standard Error 212.663
|
-955.365 pg/mL
Standard Error 174.734
|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Initial Approach)
Change at Day 56 (n=22, 29)
|
-1042.097 pg/mL
Standard Error 225.619
|
-996.485 pg/mL
Standard Error 196.729
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=46 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=45 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Extended Approach)
Change at Day 7 (n=37, 42)
|
-1207.678 pg/mL
Standard Error 133.298
|
-923.325 pg/mL
Standard Error 130.533
|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Extended Approach)
Change at Day 14 (n=36, 39)
|
-725.454 pg/mL
Standard Error 195.921
|
-705.849 pg/mL
Standard Error 192.890
|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Extended Approach)
Change at Day 28 (n=26, 38)
|
-1115.741 pg/mL
Standard Error 200.367
|
-877.871 pg/mL
Standard Error 172.950
|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Extended Approach)
Change at Day 56 (n=26, 32)
|
-860.191 pg/mL
Standard Error 206.289
|
-962.342 pg/mL
Standard Error 189.817
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=36 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=42 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Initial Approach)
Change at Day 7 (n=31, 38)
|
-174718.396 pg/mL
Standard Error 45481.710
|
-227274.816 pg/mL
Standard Error 41821.023
|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Initial Approach)
Change at Day 14 (n=30, 35)
|
-149198.139 pg/mL
Standard Error 47388.834
|
-199515.687 pg/mL
Standard Error 43965.789
|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Initial Approach)
Change at Day 28 (n=22, 35)
|
-255317.294 pg/mL
Standard Error 70915.154
|
-160587.365 pg/mL
Standard Error 57944.793
|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Initial Approach)
Change at Day 56 (n=21, 29)
|
-204731.356 pg/mL
Standard Error 50404.332
|
-223918.341 pg/mL
Standard Error 43039.568
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=46 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=45 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Extended Approach)
Change at Day 7 (n=37, 42)
|
-193222.856 pg/mL
Standard Error 39595.196
|
-215296.477 pg/mL
Standard Error 38432.424
|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Extended Approach)
Change at Day 14 (n=36, 39)
|
-172069.810 pg/mL
Standard Error 41341.330
|
-195751.307 pg/mL
Standard Error 40449.866
|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Extended Approach)
Change at Day 28 (n=26, 38)
|
-264788.038 pg/mL
Standard Error 62440.420
|
-160441.028 pg/mL
Standard Error 53963.528
|
|
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Extended Approach)
Change at Day 56 (n=25, 32)
|
-168204.970 pg/mL
Standard Error 51760.361
|
-205822.814 pg/mL
Standard Error 46476.985
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=36 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=42 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Initial Approach)
Change at Day 7 (n=31, 38)
|
-9253.786 ng/mL
Standard Error 1997.077
|
-4521.397 ng/mL
Standard Error 1863.867
|
|
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Initial Approach)
Change at Day 14 (n=30, 35)
|
-8072.784 ng/mL
Standard Error 2144.895
|
-6318.878 ng/mL
Standard Error 2002.939
|
|
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Initial Approach)
Change at Day 28 (n=22, 35)
|
-13744.824 ng/mL
Standard Error 2476.123
|
-5944.184 ng/mL
Standard Error 2041.587
|
|
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Initial Approach)
Change at Day 56 (n=22, 29)
|
-10248.612 ng/mL
Standard Error 2578.146
|
-9478.460 ng/mL
Standard Error 2234.238
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=46 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=45 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Extended Approach)
Change at Day 7 (n=37, 42)
|
-8606.357 ng/mL
Standard Error 1747.094
|
-4380.803 ng/mL
Standard Error 1713.047
|
|
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Extended Approach)
Change at Day 14 (n=36, 39)
|
-8380.855 ng/mL
Standard Error 1871.930
|
-5929.775 ng/mL
Standard Error 1843.806
|
|
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Extended Approach)
Change at Day 28 (n=26, 38)
|
-12692.279 ng/mL
Standard Error 2220.374
|
-5351.001 ng/mL
Standard Error 1933.964
|
|
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Extended Approach)
Change at Day 56 (n=26, 32)
|
-9424.227 ng/mL
Standard Error 2275.981
|
-8527.766 ng/mL
Standard Error 2078.411
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=36 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=42 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Initial Approach)
Change at Day 7 (n=31, 38)
|
-222995.020 µg/mL
Standard Error 14887.254
|
-224606.396 µg/mL
Standard Error 13669.986
|
|
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Initial Approach)
Change at Day 14 (n=30, 35)
|
-149211.318 µg/mL
Standard Error 39523.470
|
-125385.276 µg/mL
Standard Error 36629.962
|
|
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Initial Approach)
Change at Day 28 (n=22, 35)
|
-200905.068 µg/mL
Standard Error 25432.984
|
-149865.936 µg/mL
Standard Error 20549.567
|
|
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Initial Approach)
Change at Day 56 (n=21, 30)
|
-141985.838 µg/mL
Standard Error 28278.566
|
-169389.587 µg/mL
Standard Error 23767.879
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=46 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=45 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Extended Approach)
Change at Day 7 (n=37, 42)
|
-202235.344 µg/mL
Standard Error 12993.506
|
-206912.465 µg/mL
Standard Error 12543.143
|
|
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Extended Approach)
Change at Day 14 (n=36, 39)
|
-143831.510 µg/mL
Standard Error 34043.871
|
-110144.325 µg/mL
Standard Error 33211.578
|
|
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Extended Approach)
Change at Day 28 (n=26, 38)
|
-183452.324 µg/mL
Standard Error 22560.241
|
-130613.019 µg/mL
Standard Error 19255.852
|
|
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Extended Approach)
Change at Day 56 (n=25, 33)
|
-118129.436 µg/mL
Standard Error 25397.042
|
-156544.533 µg/mL
Standard Error 22550.054
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Initial Approach)
Change at Day 7 (n=37, 41)
|
-12.469 pg/mL
Standard Error 0.782
|
-11.904 pg/mL
Standard Error 0.742
|
|
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Initial Approach)
Change at Day 14 (n=33, 41)
|
-1.973 pg/mL
Standard Error 1.918
|
-5.728 pg/mL
Standard Error 1.730
|
|
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Initial Approach)
Change at Day 28 (n=28, 40)
|
-8.108 pg/mL
Standard Error 2.360
|
-7.243 pg/mL
Standard Error 1.997
|
|
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Initial Approach)
Change at Day 56 (n=27, 40)
|
-11.665 pg/mL
Standard Error 1.129
|
-9.431 pg/mL
Standard Error 0.937
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=48 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Extended Approach)
Change at Day 7 (n=47, 45)
|
-12.314 pg/mL
Standard Error 0.652
|
-11.802 pg/mL
Standard Error 0.665
|
|
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Extended Approach)
Change at Day 14 (n=43, 45)
|
1.607 pg/mL
Standard Error 2.543
|
-6.069 pg/mL
Standard Error 2.490
|
|
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Extended Approach)
Change at Day 28 (n=33, 44)
|
-7.587 pg/mL
Standard Error 2.088
|
-7.619 pg/mL
Standard Error 1.838
|
|
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Extended Approach)
Change at Day 56 (n=32, 44)
|
-10.811 pg/mL
Standard Error 1.064
|
-9.604 pg/mL
Standard Error 0.918
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Blood Biomarker Interleukin-1 Beta (IL-1β) (Initial Approach)
Change at Day 7 (n=37, 41)
|
1.274 pg/mL
Standard Error 0.682
|
0.378 pg/mL
Standard Error 0.647
|
|
Change From Baseline in Blood Biomarker Interleukin-1 Beta (IL-1β) (Initial Approach)
Change at Day 14 (n=33, 41)
|
0.217 pg/mL
Standard Error 0.359
|
0.495 pg/mL
Standard Error 0.324
|
|
Change From Baseline in Blood Biomarker Interleukin-1 Beta (IL-1β) (Initial Approach)
Change at Day 28 (n=28, 40)
|
0.657 pg/mL
Standard Error 0.431
|
0.541 pg/mL
Standard Error 0.366
|
|
Change From Baseline in Blood Biomarker Interleukin-1 Beta (IL-1β) (Initial Approach)
Change at Day 56 (n=27, 40)
|
-0.003 pg/mL
Standard Error 0.329
|
0.464 pg/mL
Standard Error 0.288
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=48 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Blood Biomarker IL-1β (Extended Approach)
Change at Day 7 (n=47, 45)
|
0.350 pg/mL
Standard Error 0.590
|
-1.002 pg/mL
Standard Error 0.602
|
|
Change From Baseline in Blood Biomarker IL-1β (Extended Approach)
Change at Day 14 (n=43, 45)
|
-0.394 pg/mL
Standard Error 0.355
|
-0.841 pg/mL
Standard Error 0.349
|
|
Change From Baseline in Blood Biomarker IL-1β (Extended Approach)
Change at Day 28 (n=33, 44)
|
-0.139 pg/mL
Standard Error 0.414
|
-0.757 pg/mL
Standard Error 0.368
|
|
Change From Baseline in Blood Biomarker IL-1β (Extended Approach)
Change at Day 56 (n=32, 44)
|
-0.799 pg/mL
Standard Error 0.333
|
-0.806 pg/mL
Standard Error 0.312
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Initial Approach)
Change at Day 7 (n=37, 41)
|
-15.579 mg/liter(L)
Standard Error 0.485
|
-16.518 mg/liter(L)
Standard Error 0.461
|
|
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Initial Approach)
Change at Day 14 (n=33, 41)
|
4.836 mg/liter(L)
Standard Error 4.249
|
-4.369 mg/liter(L)
Standard Error 3.812
|
|
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Initial Approach)
Change at Day 28 (n=28, 38)
|
-9.179 mg/liter(L)
Standard Error 4.110
|
-8.018 mg/liter(L)
Standard Error 3.533
|
|
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Initial Approach)
Change at Day 56 (n=26, 40)
|
-14.889 mg/liter(L)
Standard Error 1.395
|
-13.057 mg/liter(L)
Standard Error 1.133
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=48 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Extended Approach)
Change at Day 7 (n=47, 45)
|
-16.166 mg/L
Standard Error 0.410
|
-16.901 mg/L
Standard Error 0.417
|
|
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Extended Approach)
Change at Day 14 (n=43, 45)
|
5.720 mg/L
Standard Error 3.600
|
-5.257 mg/L
Standard Error 3.518
|
|
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Extended Approach)
Change at Day 28 (n=33, 42)
|
-8.250 mg/L
Standard Error 3.802
|
-9.254 mg/L
Standard Error 3.375
|
|
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Extended Approach)
Change at Day 56 (n=31, 44)
|
-15.152 mg/L
Standard Error 1.219
|
-13.793 mg/L
Standard Error 1.034
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=35 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=42 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Blood Biomarker Fibrinogen (Initial Approach)
Change at Day 7 (n=34, 39)
|
-3.916 umol/L
Standard Error 0.286
|
-3.976 umol/L
Standard Error 0.261
|
|
Change From Baseline in Blood Biomarker Fibrinogen (Initial Approach)
Change at Day 14 (n=33, 38)
|
0.404 umol/L
Standard Error 0.625
|
-0.184 umol/L
Standard Error 0.571
|
|
Change From Baseline in Blood Biomarker Fibrinogen (Initial Approach)
Change at Day 28 (n=27, 36)
|
0.210 umol/L
Standard Error 0.676
|
0.014 umol/L
Standard Error 0.567
|
|
Change From Baseline in Blood Biomarker Fibrinogen (Initial Approach)
Change at Day 56 (n=26, 38)
|
-2.127 umol/L
Standard Error 0.625
|
-1.144 umol/L
Standard Error 0.515
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=45 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=46 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Blood Biomarker Fibrinogen (Extended Approach)
Change at Day 7 (n=44, 43)
|
-3.971 umol/L
Standard Error 0.246
|
-3.839 umol/L
Standard Error 0.244
|
|
Change From Baseline in Blood Biomarker Fibrinogen (Extended Approach)
Change at Day 14 (n=43, 42)
|
0.051 umol/L
Standard Error 0.521
|
-0.148 umol/L
Standard Error 0.519
|
|
Change From Baseline in Blood Biomarker Fibrinogen (Extended Approach)
Change at Day 28 (n=32, 40)
|
0.147 umol/L
Standard Error 0.599
|
-0.091 umol/L
Standard Error 0.524
|
|
Change From Baseline in Blood Biomarker Fibrinogen (Extended Approach)
Change at Day 56 (n=31, 42)
|
-2.155 umol/L
Standard Error 0.533
|
-1.162 umol/L
Standard Error 0.462
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=37 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Blood Biomarker Glucose (Initial Approach)
Change at Day 7 (n=37, 41)
|
1.617 mmol/L
Standard Error 0.426
|
1.027 mmol/L
Standard Error 0.397
|
|
Change From Baseline in Blood Biomarker Glucose (Initial Approach)
Change at Day 14 (n=33, 41)
|
1.000 mmol/L
Standard Error 0.300
|
0.432 mmol/L
Standard Error 0.270
|
|
Change From Baseline in Blood Biomarker Glucose (Initial Approach)
Change at Day 28 (n=28, 40)
|
0.067 mmol/L
Standard Error 0.156
|
-0.020 mmol/L
Standard Error 0.129
|
|
Change From Baseline in Blood Biomarker Glucose (Initial Approach)
Change at Day 56 (n=27, 40)
|
0.255 mmol/L
Standard Error 0.272
|
0.226 mmol/L
Standard Error 0.230
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=47 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Blood Biomarker Glucose (Extended Approach)
Change at Day 7 (n=46, 45)
|
1.767 mmol/L
Standard Error 0.408
|
0.973 mmol/L
Standard Error 0.408
|
|
Change From Baseline in Blood Biomarker Glucose (Extended Approach)
Change at Day 14 (n=42, 45)
|
0.942 mmol/L
Standard Error 0.254
|
0.364 mmol/L
Standard Error 0.246
|
|
Change From Baseline in Blood Biomarker Glucose (Extended Approach)
Change at Day 28 (n=33, 44)
|
0.061 mmol/L
Standard Error 0.139
|
-0.008 mmol/L
Standard Error 0.119
|
|
Change From Baseline in Blood Biomarker Glucose (Extended Approach)
Change at Day 56 (n=32, 43)
|
0.189 mmol/L
Standard Error 0.235
|
0.215 mmol/L
Standard Error 0.210
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=37 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Forced Expiratory Volume (FEV1) (Initial Approach)
Change at Day 7 (n=37, 41)
|
0.051 liters
Standard Error 0.031
|
0.010 liters
Standard Error 0.029
|
|
Change From Baseline in Forced Expiratory Volume (FEV1) (Initial Approach)
Change at Day 14 (n=33, 41)
|
0.083 liters
Standard Error 0.035
|
0.028 liters
Standard Error 0.031
|
|
Change From Baseline in Forced Expiratory Volume (FEV1) (Initial Approach)
Change at Day 28 (n=28, 40)
|
0.095 liters
Standard Error 0.037
|
0.001 liters
Standard Error 0.031
|
|
Change From Baseline in Forced Expiratory Volume (FEV1) (Initial Approach)
Change at Day 56 (n=27, 40)
|
0.064 liters
Standard Error 0.039
|
0.010 liters
Standard Error 0.033
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=47 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Forced Expiratory Volume (FEV1) (Extended Approach)
Change at Day 7 (n=47, 45)
|
0.063 liters
Standard Error 0.027
|
0.012 liters
Standard Error 0.028
|
|
Change From Baseline in Forced Expiratory Volume (FEV1) (Extended Approach)
Change at Day 14 (n= 43, 45)
|
0.062 liters
Standard Error 0.029
|
0.018 liters
Standard Error 0.029
|
|
Change From Baseline in Forced Expiratory Volume (FEV1) (Extended Approach)
Change at Day 28 (n=33, 44)
|
0.084 liters
Standard Error 0.031
|
-0.003 liters
Standard Error 0.028
|
|
Change From Baseline in Forced Expiratory Volume (FEV1) (Extended Approach)
Change at Day 56 (n=32, 44)
|
0.050 liters
Standard Error 0.034
|
0.005 liters
Standard Error 0.030
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=37 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Forced Vital Capacity (FVC) (Initial Approach)
Change at Day 7 (n=37, 41)
|
0.002 liters
Standard Error 0.060
|
0.057 liters
Standard Error 0.056
|
|
Change From Baseline in Forced Vital Capacity (FVC) (Initial Approach)
Change at Day 14 (n=33, 41)
|
0.039 liters
Standard Error 0.062
|
0.166 liters
Standard Error 0.056
|
|
Change From Baseline in Forced Vital Capacity (FVC) (Initial Approach)
Change at Day 28 (n=28, 40)
|
0.039 liters
Standard Error 0.072
|
0.075 liters
Standard Error 0.062
|
|
Change From Baseline in Forced Vital Capacity (FVC) (Initial Approach)
Change at Day 56 (n=27, 40)
|
0.044 liters
Standard Error 0.072
|
0.086 liters
Standard Error 0.062
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=47 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Forced Vital Capacity (FVC) (Extended Approach)
Change at Day 7 (n=47, 45)
|
0.048 liters
Standard Error 0.052
|
0.062 liters
Standard Error 0.053
|
|
Change From Baseline in Forced Vital Capacity (FVC) (Extended Approach)
Change at Day 14 (n=43, 45)
|
0.046 liters
Standard Error 0.054
|
0.146 liters
Standard Error 0.053
|
|
Change From Baseline in Forced Vital Capacity (FVC) (Extended Approach)
Change at Day 28 (n=33, 44)
|
0.053 liters
Standard Error 0.062
|
0.067 liters
Standard Error 0.057
|
|
Change From Baseline in Forced Vital Capacity (FVC) (Extended Approach)
Change at Day 56 (n=32, 44)
|
0.034 liters
Standard Error 0.065
|
0.084 liters
Standard Error 0.058
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=37 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in FEV1/FVC (Initial Approach)
Change at Day 7 (n=37, 41)
|
1.575 percent
Standard Error 0.933
|
-1.064 percent
Standard Error 0.870
|
|
Change From Baseline in FEV1/FVC (Initial Approach)
Change at Day 14 (n=33, 41)
|
1.874 percent
Standard Error 1.012
|
-1.796 percent
Standard Error 0.914
|
|
Change From Baseline in FEV1/FVC (Initial Approach)
Change at Day 28 (n=28, 40)
|
2.350 percent
Standard Error 1.138
|
-1.029 percent
Standard Error 0.982
|
|
Change From Baseline in FEV1/FVC (Initial Approach)
Change at Day 56 (n=27, 40)
|
1.636 percent
Standard Error 0.951
|
-1.669 percent
Standard Error 0.828
|
SECONDARY outcome
Timeframe: Baseline and Day 7, Day 14, Day 28 and Day 56Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=47 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in FEV1/FVC (Extended Approach)
Change at Day 7 (n=47, 45)
|
1.282 percent
Standard Error 0.795
|
-1.128 percent
Standard Error 0.799
|
|
Change From Baseline in FEV1/FVC (Extended Approach)
Change at Day 14 (n=43, 45)
|
1.394 percent
Standard Error 0.850
|
-1.830 percent
Standard Error 0.834
|
|
Change From Baseline in FEV1/FVC (Extended Approach)
Change at Day 28 (n=33, 44)
|
2.045 percent
Standard Error 0.974
|
-1.198 percent
Standard Error 0.888
|
|
Change From Baseline in FEV1/FVC (Extended Approach)
Change at Day 56 (n=32, 44)
|
1.393 percent
Standard Error 0.827
|
-1.881 percent
Standard Error 0.765
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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).
Outcome measures
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Week 1 (n=27, 34)
|
19.4 score on a scale
Standard Deviation 6.65
|
19.2 score on a scale
Standard Deviation 7.20
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Week 2 (n=28, 36)
|
17.1 score on a scale
Standard Deviation 7.86
|
17.1 score on a scale
Standard Deviation 7.48
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Week 3 (n=24, 37)
|
15.9 score on a scale
Standard Deviation 7.84
|
16.0 score on a scale
Standard Deviation 7.90
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Week 4 (n=23, 38)
|
15.1 score on a scale
Standard Deviation 7.85
|
15.8 score on a scale
Standard Deviation 8.42
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Week 5 (n=21, 37)
|
14.2 score on a scale
Standard Deviation 7.41
|
14.9 score on a scale
Standard Deviation 8.04
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Week 6 (n=19, 37)
|
12.9 score on a scale
Standard Deviation 6.85
|
15.4 score on a scale
Standard Deviation 8.23
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Week 7 (n=20, 33)
|
13.9 score on a scale
Standard Deviation 8.93
|
14.7 score on a scale
Standard Deviation 8.48
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Week 8 (n=18, 30)
|
12.8 score on a scale
Standard Deviation 7.85
|
15.6 score on a scale
Standard Deviation 8.25
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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).
Outcome measures
| Measure |
Roflumilast 500 μg
n=48 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 1 (n=37, 38)
|
20.4 score on a scale
Standard Deviation 7.26
|
19.3 score on a scale
Standard Deviation 7.03
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 2 (n=37, 40)
|
18.2 score on a scale
Standard Deviation 8.54
|
17.2 score on a scale
Standard Deviation 7.32
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 3 (n=29, 41)
|
16.2 score on a scale
Standard Deviation 8.08
|
16.1 score on a scale
Standard Deviation 7.73
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 4 (n=27, 42)
|
16.0 score on a scale
Standard Deviation 8.21
|
15.9 score on a scale
Standard Deviation 8.26
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 5 (n=25, 41)
|
14.0 score on a scale
Standard Deviation 7.28
|
15.1 score on a scale
Standard Deviation 7.93
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 6 (n=23, 41)
|
12.9 score on a scale
Standard Deviation 6.58
|
15.4 score on a scale
Standard Deviation 8.12
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 7 (n=24, 37)
|
13.5 score on a scale
Standard Deviation 8.38
|
14.8 score on a scale
Standard Deviation 8.44
|
|
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 8 (n=19, 30)
|
13.0 score on a scale
Standard Deviation 7.68
|
15.6 score on a scale
Standard Deviation 8.25
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Change at Week 1 (n=27, 34)
|
6.448 score on a scale
Standard Error 1.503
|
2.695 score on a scale
Standard Error 1.096
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Change at Week 2 (n=28, 36)
|
3.778 score on a scale
Standard Error 1.239
|
0.804 score on a scale
Standard Error 0.911
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Change at Week 3 (n=24, 37)
|
2.002 score on a scale
Standard Error 0.915
|
0.278 score on a scale
Standard Error 0.669
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Change at Week 4 (n=23, 38)
|
0.559 score on a scale
Standard Error 0.739
|
0.277 score on a scale
Standard Error 0.536
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Change at Week 5 (n=21, 37)
|
-0.412 score on a scale
Standard Error 0.613
|
-0.392 score on a scale
Standard Error 0.448
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Change at Week 6 (n=19, 37)
|
-0.924 score on a scale
Standard Error 0.411
|
-0.062 score on a scale
Standard Error 0.297
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Change at Week 7 (n=20, 33)
|
-0.228 score on a scale
Standard Error 0.342
|
0.048 score on a scale
Standard Error 0.253
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Change at Week 8 (n=18, 30)
|
0.002 score on a scale
Standard Error 0.059
|
-0.048 score on a scale
Standard Error 0.044
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=48 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 1 (n=37, 38)
|
6.232 scores on a scale
Standard Error 1.424
|
3.009 scores on a scale
Standard Error 1.052
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 2 (n=37, 40)
|
3.558 scores on a scale
Standard Error 1.178
|
1.074 scores on a scale
Standard Error 0.876
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 3 (n=29, 41)
|
2.044 scores on a scale
Standard Error 0.847
|
0.458 scores on a scale
Standard Error 0.627
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 4 (n=27, 42)
|
0.545 scores on a scale
Standard Error 0.732
|
0.429 scores on a scale
Standard Error 0.534
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 5 (n=25, 41)
|
-0.347 scores on a scale
Standard Error 0.621
|
-0.170 scores on a scale
Standard Error 0.459
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 6 (n=23, 41)
|
-0.668 scores on a scale
Standard Error 0.402
|
-0.043 scores on a scale
Standard Error 0.295
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 7 (n=24, 37)
|
-0.121 scores on a scale
Standard Error 0.310
|
0.014 scores on a scale
Standard Error 0.232
|
|
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Week 8 (n=19, 30)
|
-0.010 scores on a scale
Standard Error 0.061
|
-0.031 scores on a scale
Standard Error 0.045
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Week 1 (n=25, 35)
|
45.2 score on a scale
Standard Deviation 8.54
|
45.1 score on a scale
Standard Deviation 8.50
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Week 2 (n=28, 36)
|
41.2 score on a scale
Standard Deviation 11.39
|
42.4 score on a scale
Standard Deviation 9.07
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Week 3 (n=24, 38)
|
38.8 score on a scale
Standard Deviation 11.22
|
40.0 score on a scale
Standard Deviation 10.22
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Week 4 (n=23, 38)
|
38.3 score on a scale
Standard Deviation 11.00
|
40.2 score on a scale
Standard Deviation 11.26
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Week 5 (n=21, 37)
|
35.9 score on a scale
Standard Deviation 11.11
|
39.1 score on a scale
Standard Deviation 10.55
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Week 6 (n=19, 37)
|
35.1 score on a scale
Standard Deviation 9.75
|
39.4 score on a scale
Standard Deviation 11.05
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Week 7 (n=20, 34)
|
35.6 score on a scale
Standard Deviation 13.69
|
38.7 score on a scale
Standard Deviation 12.05
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Week 8 (n=18, 32)
|
34.4 score on a scale
Standard Deviation 11.50
|
39.4 score on a scale
Standard Deviation 11.34
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=48 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 1 (n=35, 39)
|
45.6 score on a scale
Standard Deviation 9.19
|
45.0 score on a scale
Standard Deviation 8.39
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 2 (n=37, 40)
|
42.0 score on a scale
Standard Deviation 11.07
|
42.3 score on a scale
Standard Deviation 8.81
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 3 (n=29, 42)
|
39.0 score on a scale
Standard Deviation 11.27
|
39.9 score on a scale
Standard Deviation 9.82
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 4 (n=27, 42)
|
38.8 score on a scale
Standard Deviation 11.37
|
40.3 score on a scale
Standard Deviation 10.90
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 5 (n=25, 41)
|
35.3 score on a scale
Standard Deviation 11.03
|
39.1 score on a scale
Standard Deviation 10.13
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 6 (n=23, 41)
|
33.9 score on a scale
Standard Deviation 10.45
|
39.4 score on a scale
Standard Deviation 10.62
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 7 (n=24, 38)
|
34.3 score on a scale
Standard Deviation 13.09
|
38.7 score on a scale
Standard Deviation 11.52
|
|
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 8 (n=19, 33)
|
34.0 score on a scale
Standard Deviation 11.30
|
39.6 score on a scale
Standard Deviation 11.25
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Change at Week 1 (n=25, 35)
|
6.182 score on a scale
Standard Error 3.271
|
4.753 score on a scale
Standard Error 2.385
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Change at Week 2 (n=28, 36)
|
4.423 score on a scale
Standard Error 2.538
|
1.558 score on a scale
Standard Error 1.864
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Change at Week 3 (n=24, 38)
|
2.080 score on a scale
Standard Error 2.041
|
0.317 score on a scale
Standard Error 1.494
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Change at Week 4 (n=23, 38)
|
0.002 score on a scale
Standard Error 2.003
|
0.657 score on a scale
Standard Error 1.459
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Change at Week 5 (n=21, 37)
|
-1.058 score on a scale
Standard Error 1.748
|
-0.307 score on a scale
Standard Error 1.276
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Change at Week 6 (n=19, 37)
|
-1.688 score on a scale
Standard Error 1.015
|
-0.002 score on a scale
Standard Error 0.738
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Change at Week 7 (n=20, 34)
|
-0.773 score on a scale
Standard Error 0.698
|
0.002 score on a scale
Standard Error 0.514
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
Change at Week 8 (n=18, 32)
|
-0.190 score on a scale
Standard Error 0.259
|
-0.154 score on a scale
Standard Error 0.191
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=48 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 1 (n=35, 39)
|
7.163 scores on a scale
Standard Error 2.859
|
4.697 scores on a scale
Standard Error 2.077
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 2 (n=37, 40)
|
4.839 scores on a scale
Standard Error 2.259
|
1.433 scores on a scale
Standard Error 1.652
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 3 (n=29, 42)
|
2.988 scores on a scale
Standard Error 1.870
|
0.179 scores on a scale
Standard Error 1.363
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 4 (n=27, 42)
|
0.909 scores on a scale
Standard Error 1.861
|
0.743 scores on a scale
Standard Error 1.344
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 5 (n=25, 41)
|
-0.657 scores on a scale
Standard Error 1.554
|
-0.318 scores on a scale
Standard Error 1.129
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 6 (n=23, 41)
|
-0.889 scores on a scale
Standard Error 0.976
|
-0.140 scores on a scale
Standard Error 0.706
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 7 (n=24, 38)
|
-0.311 scores on a scale
Standard Error 0.654
|
-0.075 scores on a scale
Standard Error 0.479
|
|
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
Week 8 9n=19, 33)
|
-0.240 scores on a scale
Standard Error 0.244
|
-0.115 scores on a scale
Standard Error 0.178
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach)
Change at Week 1 (n=37, 38)
|
-16.551 liters/minute
Standard Error 5.144
|
-9.915 liters/minute
Standard Error 4.442
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach)
Change at Week 2 (n=35, 40)
|
-6.067 liters/minute
Standard Error 4.564
|
-0.304 liters/minute
Standard Error 3.899
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach)
Change at Week 3 (n=35, 40)
|
-4.996 liters/minute
Standard Error 3.914
|
0.687 liters/minute
Standard Error 3.360
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach)
Change at Week 4 (n=29, 39)
|
-4.595 liters/minute
Standard Error 3.421
|
-0.420 liters/minute
Standard Error 2.737
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach)
Change at Week 5 (n=28, 38)
|
-3.557 liters/minute
Standard Error 4.061
|
-1.224 liters/minute
Standard Error 3.287
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach)
Change at Week 6 (n=27, 37)
|
-3.795 liters/minute
Standard Error 4.546
|
-5.559 liters/minute
Standard Error 3.680
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach)
Change at Week 7 (n=27, 36)
|
-7.178 liters/minute
Standard Error 5.212
|
-4.186 liters/minute
Standard Error 4.264
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach)
Change at Week 8 (n=27, 35)
|
-2.877 liters/minute
Standard Error 5.388
|
-0.956 liters/minute
Standard Error 4.418
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=48 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach)
Change at Week 1 (n=46, 42)
|
-13.958 liters/minute
Standard Error 4.147
|
-8.447 liters/minute
Standard Error 3.865
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach)
Change at Week 2 (n=44, 44)
|
-5.776 liters/minute
Standard Error 3.772
|
1.029 liters/minute
Standard Error 3.488
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach)
Change at Week 3 (n=44, 44)
|
-5.360 liters/minute
Standard Error 3.676
|
2.038 liters/minute
Standard Error 3.421
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach)
Change at Week 4 (n=37, 43)
|
-6.660 liters/minute
Standard Error 3.546
|
1.133 liters/minute
Standard Error 3.126
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach)
Change at Week 5 (n=33, 42)
|
-5.568 liters/minute
Standard Error 3.847
|
0.269 liters/minute
Standard Error 3.396
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach)
Change at Week 6 (n=32, 41)
|
-2.186 liters/minute
Standard Error 3.515
|
-4.596 liters/minute
Standard Error 3.076
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach)
Change at Week 7 (n=31, 40)
|
-8.513 liters/minute
Standard Error 4.544
|
-1.974 liters/minute
Standard Error 3.952
|
|
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach)
Change at Week 8 (n=31, 39)
|
-4.563 liters/minute
Standard Error 4.741
|
0.950 liters/minute
Standard Error 4.091
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach)
Change at Week 1 (n=38, 42)
|
2.930 score on a scale
Standard Error 0.286
|
2.587 score on a scale
Standard Error 0.254
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach)
Change at Week 2 (n=37, 42)
|
1.130 score on a scale
Standard Error 0.314
|
1.331 score on a scale
Standard Error 0.272
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach)
Change at Week 3 (n=35, 42)
|
0.906 score on a scale
Standard Error 0.299
|
0.790 score on a scale
Standard Error 0.258
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach)
Change at Week 4 (n=30, 40)
|
0.552 score on a scale
Standard Error 0.298
|
0.922 score on a scale
Standard Error 0.248
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach)
Change at Week 5 (n=29, 39)
|
0.413 score on a scale
Standard Error 0.305
|
0.882 score on a scale
Standard Error 0.254
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach)
Change at Week 6 (n=28, 39)
|
0.141 score on a scale
Standard Error 0.310
|
0.681 score on a scale
Standard Error 0.258
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach)
Change at Week 7 (n=27, 37)
|
0.442 score on a scale
Standard Error 0.294
|
0.673 score on a scale
Standard Error 0.243
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach)
Change at Week 8 (n=27, 36)
|
0.626 score on a scale
Standard Error 0.361
|
0.612 score on a scale
Standard Error 0.297
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=48 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach)
Change at Week 2 (n=47, 46)
|
1.171 score on a scale
Standard Error 0.285
|
1.402 score on a scale
Standard Error 0.267
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach)
Change at Week 1 (n=48, 46)
|
3.110 score on a scale
Standard Error 0.257
|
2.593 score on a scale
Standard Error 0.246
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach)
Change at Week 3 (n=44, 46)
|
0.850 score on a scale
Standard Error 0.267
|
0.802 score on a scale
Standard Error 0.250
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach)
Change at Week 4 (n=38, 44)
|
0.751 score on a scale
Standard Error 0.312
|
0.924 score on a scale
Standard Error 0.282
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach)
Change at Week 5 (n=34, 43)
|
0.437 score on a scale
Standard Error 0.287
|
0.907 score on a scale
Standard Error 0.259
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach)
Change at Week 6 (n=33, 43)
|
0.041 score on a scale
Standard Error 0.257
|
0.661 score on a scale
Standard Error 0.231
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach)
Change at Week 7 (n=31, 41)
|
0.503 score on a scale
Standard Error 0.247
|
0.533 score on a scale
Standard Error 0.216
|
|
Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach)
Change at Week 8 (n=31, 40)
|
0.451 score on a scale
Standard Error 0.274
|
0.530 score on a scale
Standard Error 0.237
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach)
Change at Week 1 (n=38, 42)
|
0.849 score on a scale
Standard Error 0.194
|
0.769 score on a scale
Standard Error 0.174
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach)
Change at Week 2 (n=37, 42)
|
0.682 score on a scale
Standard Error 0.190
|
0.804 score on a scale
Standard Error 0.167
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach)
Change at Week 3 (n=35, 42)
|
0.281 score on a scale
Standard Error 0.115
|
0.188 score on a scale
Standard Error 0.099
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach)
Change at Week 4 (n=30, 40)
|
0.185 score on a scale
Standard Error 0.118
|
0.217 score on a scale
Standard Error 0.099
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach)
Change at Week 5 (n=29, 39)
|
0.130 score on a scale
Standard Error 0.123
|
0.263 score on a scale
Standard Error 0.103
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach)
Change at Week 6 (n=28, 39)
|
0.128 score on a scale
Standard Error 0.130
|
0.204 score on a scale
Standard Error 0.108
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach)
Change at Week 7 (n=27, 37)
|
0.112 score on a scale
Standard Error 0.117
|
0.135 score on a scale
Standard Error 0.097
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach)
Change at Week 8 (n=27, 36)
|
0.122 score on a scale
Standard Error 0.101
|
0.127 score on a scale
Standard Error 0.084
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=48 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach)
Change at Week 1 (n=48, 46)
|
0.787 score on a scale
Standard Error 0.170
|
0.730 score on a scale
Standard Error 0.162
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach)
Change at Week 2 (n=47, 46)
|
0.767 score on a scale
Standard Error 0.172
|
0.780 score on a scale
Standard Error 0.161
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach)
Change at Week 3 (n=44, 46)
|
0.338 score on a scale
Standard Error 0.103
|
0.177 score on a scale
Standard Error 0.095
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach)
Change at Week 4 (n=38, 44)
|
0.379 score on a scale
Standard Error 0.144
|
0.206 score on a scale
Standard Error 0.129
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach)
Change at Week 5 (n=34, 43)
|
0.191 score on a scale
Standard Error 0.107
|
0.244 score on a scale
Standard Error 0.096
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach)
Change at Week 6 (n=33, 43)
|
0.127 score on a scale
Standard Error 0.107
|
0.196 score on a scale
Standard Error 0.096
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach)
Change at Week 7 (n=31, 41)
|
0.179 score on a scale
Standard Error 0.116
|
0.156 score on a scale
Standard Error 0.103
|
|
Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach)
Change at Week 8 (n=31, 40)
|
0.084 score on a scale
Standard Error 0.086
|
0.171 score on a scale
Standard Error 0.075
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach)
Change at Week 1 (n=34, 34)
|
-1.313 hours
Standard Error 0.416
|
-0.105 hours
Standard Error 0.391
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach)
Change at Week 2 (n=34, 38)
|
-0.974 hours
Standard Error 0.359
|
-0.328 hours
Standard Error 0.333
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach)
Change at Week 3 (n=34, 40)
|
-1.077 hours
Standard Error 0.374
|
0.226 hours
Standard Error 0.335
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach)
Change at Week 4 (n=28, 39)
|
-1.131 hours
Standard Error 0.414
|
-0.306 hours
Standard Error 0.354
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach)
Change at Week 5 (n=26, 38)
|
-0.826 hours
Standard Error 0.465
|
0.280 hours
Standard Error 0.407
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach)
Change at Week 6 (n=25, 35)
|
-1.154 hours
Standard Error 0.448
|
-0.062 hours
Standard Error 0.386
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach)
Change at Week 7 (n=26, 35)
|
-1.194 hours
Standard Error 0.449
|
-0.340 hours
Standard Error 0.394
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach)
Change at Week 8 (n=26, 34)
|
-0.812 hours
Standard Error 0.532
|
0.037 hours
Standard Error 0.458
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=48 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach)
Change at Week 1 (n=42, 38)
|
-1.472 hours
Standard Error 0.353
|
-0.276 hours
Standard Error 0.344
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach)
Change at Week 2 (n=43, 42)
|
-1.305 hours
Standard Error 0.319
|
-0.472 hours
Standard Error 0.307
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach)
Change at Week 3 (n=42, 44)
|
-1.314 hours
Standard Error 0.343
|
0.099 hours
Standard Error 0.324
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach)
Change at Week 4 (n=35, 43)
|
-1.328 hours
Standard Error 0.357
|
-0.266 hours
Standard Error 0.325
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach)
Change at Week 5 (n=31, 42)
|
-0.833 hours
Standard Error 0.402
|
0.158 hours
Standard Error 0.369
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach)
Change at Week 6 (n=30, 39)
|
-1.271 hours
Standard Error 0.372
|
-0.247 hours
Standard Error 0.344
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach)
Change at Week 7 (n=30, 39)
|
-1.144 hours
Standard Error 0.363
|
-0.478 hours
Standard Error 0.333
|
|
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach)
Change at Week 8 (n=30, 38)
|
-0.714 hours
Standard Error 0.443
|
-0.068 hours
Standard Error 0.401
|
SECONDARY outcome
Timeframe: 8 WeeksPopulation: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=38 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=43 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Exacerbation Length (Initial Approach)
|
12.0 days
Interval 8.0 to 18.0
|
14.0 days
Interval 10.0 to 17.0
|
SECONDARY outcome
Timeframe: 8 WeeksPopulation: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=48 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=47 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Exacerbation Length (Extended Approach)
|
13.0 days
Interval 9.0 to 19.0
|
14.0 days
Interval 11.0 to 17.0
|
SECONDARY outcome
Timeframe: Baseline and Days 14 and 28Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=24 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=28 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Initial Approach)
Change at Day 14 (n=18, 24)
|
-0.047 meters/second
Standard Error 0.337
|
-0.343 meters/second
Standard Error 0.290
|
|
Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Initial Approach)
Change at Day 28 (n=14, 24)
|
-0.380 meters/second
Standard Error 0.413
|
-0.474 meters/second
Standard Error 0.321
|
SECONDARY outcome
Timeframe: Baseline and Days 14 and 28Population: 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.
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.
Outcome measures
| Measure |
Roflumilast 500 μg
n=34 Participants
Roflumilast 500 µg tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
Placebo
n=32 Participants
Placebo matching roflumilast tablet, once daily, orally in the morning after breakfast for 4 weeks added on to standard therapy for acute COPD exacerbations.
|
|---|---|---|
|
Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Extended Approach)
Change at Day 14 (n=28, 28)
|
-0.128 meters/second
Standard Error 0.247
|
-0.326 meters/second
Standard Error 0.245
|
|
Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Extended Approach)
Change at Day 28 (n=19, 28)
|
-0.316 meters/second
Standard Error 0.323
|
-0.511 meters/second
Standard Error 0.273
|
Adverse Events
Roflumilast 500 μg (Initial Approach)
Placebo (Initial Approach)
Roflumilast 500 µg (Extended Approach)
Placebo (Extended Approach)
Serious adverse events
| Measure |
Roflumilast 500 μg (Initial Approach)
n=38 participants at risk
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.
|
Placebo (Initial Approach)
n=43 participants at risk
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.
|
Roflumilast 500 µg (Extended Approach)
n=48 participants at risk
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.
|
Placebo (Extended Approach)
n=47 participants at risk
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.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
2.6%
1/38 • 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.
|
0.00%
0/43 • 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.
|
2.1%
1/48 • 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.
|
0.00%
0/47 • 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.
|
|
Infections and infestations
Pneumonia
|
2.6%
1/38 • 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.
|
0.00%
0/43 • 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.
|
2.1%
1/48 • 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.
|
0.00%
0/47 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.6%
1/38 • 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.
|
0.00%
0/43 • 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.
|
2.1%
1/48 • 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.
|
0.00%
0/47 • 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.
|
|
Cardiac disorders
Supraventricular tachycardia
|
2.6%
1/38 • 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.
|
0.00%
0/43 • 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.
|
2.1%
1/48 • 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.
|
0.00%
0/47 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/38 • 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.
|
2.3%
1/43 • 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.
|
0.00%
0/48 • 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.
|
2.1%
1/47 • 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.
|
Other adverse events
| Measure |
Roflumilast 500 μg (Initial Approach)
n=38 participants at risk
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.
|
Placebo (Initial Approach)
n=43 participants at risk
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.
|
Roflumilast 500 µg (Extended Approach)
n=48 participants at risk
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.
|
Placebo (Extended Approach)
n=47 participants at risk
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.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
65.8%
25/38 • 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.
|
23.3%
10/43 • 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.
|
66.7%
32/48 • 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.
|
23.4%
11/47 • 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.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.3%
2/38 • 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.
|
2.3%
1/43 • 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.
|
6.2%
3/48 • 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.
|
2.1%
1/47 • 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.
|
|
Gastrointestinal disorders
Nausea
|
15.8%
6/38 • 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.
|
7.0%
3/43 • 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.
|
18.8%
9/48 • 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.
|
6.4%
3/47 • 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.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/38 • 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.
|
0.00%
0/43 • 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.
|
6.2%
3/48 • 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.
|
2.1%
1/47 • 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.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
10.5%
4/38 • 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.
|
4.7%
2/43 • 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.
|
12.5%
6/48 • 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.
|
4.3%
2/47 • 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.
|
|
Nervous system disorders
Dizziness
|
15.8%
6/38 • 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.
|
2.3%
1/43 • 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.
|
12.5%
6/48 • 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.
|
2.1%
1/47 • 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.
|
|
Nervous system disorders
Headache
|
7.9%
3/38 • 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.
|
4.7%
2/43 • 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.
|
8.3%
4/48 • 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.
|
4.3%
2/47 • 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.
|
|
Psychiatric disorders
Insomnia
|
31.6%
12/38 • 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.
|
4.7%
2/43 • 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.
|
29.2%
14/48 • 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.
|
4.3%
2/47 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
44.7%
17/38 • 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.
|
30.2%
13/43 • 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.
|
39.6%
19/48 • 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.
|
31.9%
15/47 • 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.
|
|
Gastrointestinal disorders
Abdominal pain
|
5.3%
2/38 • 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.
|
2.3%
1/43 • 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.
|
0.00%
0/48 • 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.
|
0.00%
0/47 • 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.
|
|
Gastrointestinal disorders
Flatulence
|
5.3%
2/38 • 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.
|
0.00%
0/43 • 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.
|
0.00%
0/48 • 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.
|
0.00%
0/47 • 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.
|
|
Infections and infestations
Cellulitis
|
5.3%
2/38 • 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.
|
0.00%
0/43 • 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.
|
0.00%
0/48 • 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.
|
0.00%
0/47 • 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.
|
|
Infections and infestations
Oral candidiasis
|
5.3%
2/38 • 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.
|
0.00%
0/43 • 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.
|
0.00%
0/48 • 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.
|
0.00%
0/47 • 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.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.3%
2/38 • 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.
|
0.00%
0/43 • 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.
|
0.00%
0/48 • 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.
|
0.00%
0/47 • 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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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER