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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1150-2477 | Other Identifier | World Health Organization | |
| 2013-001788-21 | EudraCT Number |
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The purpose of this study is to evaluate discontinuation rates of roflumilast using an up-titration regimen for the first 4 weeks of treatment compared with continuous treatment of 500 μg one daily (OD) during the entire 12-week main period, and to evaluate if participants who do not tolerate roflumilast 500 μg OD have a drug exposure with 250 μg roflumilast OD similar to that observed in other participants with the 500 μg OD dose.
Roflumilast is a product which has been approved for the treatment of severe chronic obstructive lung disease (COPD) and its approved dose is 500μg once daily. This study is primarily designed to see whether alternation in this dose can improve tolerability of Roflumilast in COPD patients. Therefore one in three patients will start roflumilast therapy at a lower dose of 250μg once daily, another one in three will only take the 500μg tablet every other day (and one placebo every other day). Rest of them will start the regular dose of 500μg once daily right away and see whether starting with a lower dose of Roflumilast will lead to better tolerability. Furthermore, the study will see if patients who do not tolerate roflumilast should be given a lower dose of 250μg once daily.
Lastly, the study will investigate what the body does to roflumilast. Patients with a history of COPD for at least last 12 months and a former smoker or current smoker with history of at least 10 pack years will be invited to participate.
The main study period lasts for a maximum of 15 weeks and patients will have to visit the study site up to 6 times. If patients are not tolerating roflumilast, the investigators may switch them to the down titration period where they may be on a lower dose for rest of the study. Then patients will remain in the down titration period for additional 8 weeks and will have to visit the study site 4 times. Most of the visits will take approximately 1 to 2 hours. However, one visit in the main period and 1 or 2 visits in the down titration period will take approximately 6 to 7 hours. These visits are longer to allow time to conduct blood taking.
The Randomization visit is considered the Baseline visit and for participants that discontinue the Main Period and continue into the Down-Titration Period Day 1 of Down Titration is considered BaselineDT.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Roflumilast 500 μg once daily | Experimental | Roflumilast 500 μg tablets, orally, once daily for 12 weeks. Any participants not tolerating study treatment will be prematurely discontinued and will receive roflumilast 250 μg, tablets, orally, once daily for 8 weeks. |
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| Roflumilast 500 μg every other day | Experimental | Roflumilast 500 μg, tablets, orally, every other day, and roflumilast placebo-matching tablets, orally, every other day on non-treatment days, for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks. Any participants not tolerating study treatment will be prematurely discontinued and will receive roflumilast 250 μg, tablets, orally, once daily for 8 weeks. |
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| Roflumilast 250 μg once daily | Experimental | Roflumilast 250 μg, tablets, orally, once daily for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks. Any participants not tolerating study treatment will be prematurely discontinued and will receive roflumilast 250 μg, tablets, orally, once daily for 8 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Roflumilast | Drug | Roflumilast tablets |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Prematurely Discontinuing Study Treatment Due to Any Reason | The primary endpoint is the percentage of participants prematurely discontinuing study treatment for any reason during the Main Period from Visit 1 (V1) to Last Visit (Vend). Discontinuation is defined as permanently stopping randomized treatment; participants who resume randomized treatment after an interval will not be counted as having discontinued. The analysis used discontinuations occurring during the Main Period, irrespective of whether a participant subsequently entered into the Down-Titration Period. | Baseline to Week 12 (Main Period) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Adverse Events of Interest | Adverse events of interest to evaluate tolerability are defined as diarrhea, nausea, headache, decreased appetite, insomnia and abdominal pain. | Baseline to Week 12 (Main Period) |
| Change From Baseline (V0DT) in Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) to Final Visit of the Down-Titration Period |
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Inclusion Criteria:
Exclusion Criteria:
Criteria affecting the read-out parameters of the study
Has a COPD exacerbation ongoing at the Screening (Visit V0), or has a COPD exacerbation between V0 and V1.
Has a lower respiratory tract infection not resolved 4 weeks prior to Screening (Visit V0).
Has a diagnosis of asthma and/or other relevant lung disease (eg, history of primary bronchiectases, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease [eg, fibrosis, silicosis, sarcoidosis], or active tuberculosis).
Has a known α1-antitrypsin deficiency.
Has taken roflumilast within 6 months of Screening (Visit V0).
Criteria within ethical considerations in terms of general health
Has clinically relevant abnormal laboratory values suggesting an undiagnosed disease requiring further clinical evaluation (as assessed by the investigator).
Has a history of severe psychiatric or neurological disorders.
Has a history of depression associated with suicidal ideation or behavior.
Has congestive heart failure severity grade IV according to New York Heart Association (NYHA) Functional Classification.
Has hemodynamically significant cardiac arrhythmias or heart valve deformations.
Has computed tomography (CT) or chest x-ray findings indicating an acute pulmonary disease other than COPD (eg, tuberculosis, severe bronchiectasis, tumors).
Has severe immunological diseases (eg, known human immune deficiency virus (HIV) infection, multiple sclerosis, lupus erythematosus, progressive multifocal leukoencephalopathy).
Has liver impairment Child-Pugh B or C and/or active viral hepatitis.
Has severe acute infectious diseases (eg, tuberculosis, or acute hepatitis).
Has a history of malignant disease (except basal cell carcinoma) within 5 years before Screening (Visit V0).
Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within one year before Screening (Visit V0).
Has a history of hypersensitivity or allergies to roflumilast or rescue medication or ingredients thereof, or any other contraindication for the use thereof.
If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study; or intending to donate ova during such time period.
Intends to donate blood, organs, or bone marrow during the course of the study.
Has received any investigational compound within 30 days prior to Screening (Visit V0), is currently participating in another interventional clinical study, or has been previously enrolled in this study.
Is suspected to be unable or unwilling to comply with study procedures (eg, language problems, psychological disorders, number and timing of visits at the center).
Suffers from any concomitant disease that might interfere with study procedures or evaluations.
Is required to take excluded medications.
Is an immediate family member, study center employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling), or may consent under duress.
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| Name | Affiliation | Role |
|---|---|---|
| AstraZeneca AstraZeneca | AstraZeneca | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bardejov | Slovakia | |||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29797235 | Derived | Facius A, Marostica E, Gardiner P, Watz H, Lahu G. Pharmacokinetic and Pharmacodynamic Modelling to Characterize the Tolerability of Alternative Up-Titration Regimens of Roflumilast in Patients with Chronic Obstructive Pulmonary Disease. Clin Pharmacokinet. 2018 Aug;57(8):1029-1038. doi: 10.1007/s40262-018-0671-4. |
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Participants with a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) were enrolled equally in 1 of 3 treatment groups in the Main Treatment Period: roflumilast 250 μg then 500 μg once daily (OD), 500 μg every other day (EOD) then 500 μg OD and 500 μg OD. Participants who discontinued received 250 μg in the Down-Titration Period.
Participants took part in the study at 161 investigative sites in Bulgaria, Germany, Greece, Hungary, Korea, Philippines, Poland, Romania, Russia, Slovakia, South Africa, Spain, Thailand, Ukraine and the United Kingdom from 30 April 2014 to 21 October 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | Roflumilast 250 μg OD Then 500 μg OD | Roflumilast 250 μg, tablets, orally, once daily (OD) for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks in the Main Treatment Period. Any participants not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Main Treatment Period |
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| Roflumilast Placebo | Drug | Roflumilast placebo-matching tablets |
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| Standard of Care COPD Treatment | Drug | The participant is on standard of care COPD maintenance treatment including LABAs, long-acting anticholinergics, or any combination thereof taken on a constant daily dose within 12 weeks prior to Screening (Visit V0) Examples of LABA containing products are: Formoterol, Salmeterol, Indacaterol, Formoterol/Budesonide, Salmeterol/Fluticasone, Treatment including lon-acting anticholinergics: Tiotropium, Aclidinium. |
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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 prior to taking study medication A positive change from Baseline indicates improvement. |
| Baseline (V0DT) [assessment at end of main period] and Final Visit of Down-Titration Period (Up to Day 56) |
| Percentage of Participants Prematurely Discontinuing Study Treatment Due to Any Reason During Down-Titration Period | Baseline DT (Day 1 of Down-Titration Period) to Week 8 (Down-Titration Period) |
| Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) During the Down-Titration Period | 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 prior to taking study medication. A positive change from Baseline indicates improvement. | Baseline DT (Day 1 of Down-Titration Period) to Days 14, 28 and 56 (Down-Titration Period) |
| Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) During the Main Period | 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 prior to taking study medication. A positive change from Baseline indicates improvement. | Baseline (Day 1 of Main Period) to Days 15, 29, 57 and 84 (Main Period) |
| Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) During the Main Period | 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 prior to taking study medication. A positive change from Baseline indicates improvement. | Baseline (Day 1 of Main Period) to Days 15, 29, 57 and 84 (Main Period) |
| Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) During the Down-Titration Period | 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 prior to taking study medication. A positive change from Baseline indicates improvement. | Baseline DT (Day 1 of Down-Titration Period) to Days 14, 28 and 56 (Down-Titration Period) |
| Change From Baseline in Treatment Satisfaction Scores During the Main Period | Participants will be asked to assess their satisfaction with their COPD therapy at each visit. The participants will rate their treatment satisfaction on a 7-point scale where 0=very satisfied, 1=satisfied, 2=somewhat satisfied, 3=neither satisfied nor dissatisfied, 4=somewhat dissatisfied, 5=dissatisfied and 6=very dissatisfied. A negative change from Baseline indicates improvement. | Baseline (Day 1 of Main Period) to Days 15, 29, 57 and 84 (Main Period) |
| Change From Baseline in Treatment Satisfaction Scores During the Down-Titration Period | Participants will be asked to assess their satisfaction with their COPD therapy at each visit. The participants will rate their treatment satisfaction on a 7-point scale where 0=very satisfied, 1=satisfied, 2=somewhat satisfied, 3=neither satisfied nor dissatisfied, 4=somewhat dissatisfied, 5=dissatisfied and 6=very dissatisfied. A negative change from Baseline indicates improvement. | Baseline DT (Day 1 of Down-Titration Period) to Days 14, 28 and 56 (Down-Titration Period) |
| Population PK Model Point Estimate for Absorption Rate Constant (Ka) of Roflumilast and Roflumilast N-oxide | PK model point estimates for Ka are calculated using all available PK data for all doses of roflumilast combined and are presented for roflumilast and metabolite roflumilast N-oxide. Results are reported for the subgroups defined according to the covariates (weight, age, smoking status and sex) included in the final model. | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours at weeks 2 or 8 |
| Population PK Model Point Estimate for Apparent Oral Clearance (CL/F) of Roflumilast and Roflumilast N-oxide | PK model point estimates for CL/F are calculated using all available PK data for all doses of roflumilast combined and are presented for roflumilast and metabolite roflumilast N-oxide. Results are reported for the subgroups defined according to the covariates (weight, age, smoking status and sex) included in the final model. | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours at weeks 2 or 8 |
| Population PK Model Point Estimate for Apparent Central Volume (Vc/F) of Roflumilast and Roflumilast N-oxide | PK model point estimates for Vc/F are calculated using all available PK data for all doses of roflumilast combined and are presented for roflumilast and metabolite roflumilast N-oxide. Results are reported for the subgroups defined according to the covariates (weight, age, smoking status and sex) included in the final model. | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours at weeks 2 or 8 |
| Population PK Model Point Estimate for Apparent Peripheral Volume (Vp/F) of Roflumilast and Roflumilast N-oxide | PK model point estimates for Vp/F are calculated using all available PK data for all doses of roflumilast combined and are presented for roflumilast and metabolite roflumilast N-oxide. Results are reported for the subgroups defined according to the covariates (weight, age, smoking status and sex) included in the final model. | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours at weeks 2 or 8 |
| Total PDE4 Inhibitory Activity (tPDE4i) | tPDE4i was derived using in-vitro constants for protein binding and biochemical activity (IC50). tPDE4i is reported for a set of reference participants defined according to the covariates included in the final model. | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours post-dose at Days 15 and 57. Down-titration: Pre-dose and 1,2,3,4,6 hours post-dose at Days 1 and 14 and pre-dose at Days 28 and 56. |
| Summary Statistics of Predicted Total PDE4 Inhibitory Activity (tPDE4i) | tPDE4i was derived using in-vitro constants for protein binding and biochemical activity (IC50). An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. Adverse Events of Interest (AEI) for PK analyses included: headache, diarrhea, nausea, vomiting, abdominal pain, appetite disorders, sleep disorders, angioedema, psychiatric disorders (anxiety, nervousness), psychiatric disorders (depression,suicidal ideation,behaviour) and weight loss. | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours post-dose at Days 15 and 57. Down-titration: Pre-dose and 1,2,3,4,6 hours post-dose at Days 1 and 14 and pre-dose at Days 28 and 56. |
| Median Simulated Percentage of Participants With Adverse Events of Interest | The PK model predicted the total PDE4 inhibitory activity and the median simulated percentage of participants with Adverse Events of Interest during 12 weeks of treatment based on 1000 participants simulated. Results are reported for the set of reference participants defined according to the covariates [weight, smoking status, sex, age and long acting muscarinic antagonist (LAMA)] included in the final model and tPDE4i. Adverse Events of Interest (AEI) for PK analyses included: headache, diarrhea, nausea, vomiting, abdominal pain, appetite disorders, sleep disorders, angioedema, psychiatric disorders (anxiety, nervousness), psychiatric disorders (depression, suicidal ideation, behaviour) and weight loss. | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours post-dose at Days 15 and 57. AEIs: 12 Weeks |
| Median Simulated Absolute Change From Baseline in FEV1 at Weeks 4 and 12 | The PK model predicted the total PDE4 inhibitory activity and the median simulated Change from Baseline (CFB) in FEV1 at Week 4 and the Change from Baseline in FEV1 at Week 12 during 12 weeks of treatment with roflumilast 500 μg OD based on 1000 participants simulated. Results are reported for the set of reference participants defined according to the covariates [weight, smoking status, sex, age, race, COPD severity, concomitant long acting muscarinic antagonist (LAMA) and Percent FEV1 reversibility] included in the final model and tPDE4i. 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 prior to taking study medication. A positive change from Baseline indicates improvement. | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours post-dose at Days 15 and 57. FEV-1: Pre-dose and Weeks 4 and 12 |
| Spišská Nová Ves |
| Slovakia |
| FG001 | Roflumilast 500 μg EOD Then 500 μg OD | Roflumilast 500 μg, tablets, orally, every other day (EOD), and roflumilast placebo-matching tablets, orally, every other day on non-treatment days, for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks in the Main Treatment Period. Any participants not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. |
| FG002 | Roflumilast 500 μg OD | Roflumilast 500 μg, tablets, orally, once daily (OD) at least 1 dose in the Main Period. |
| Safety Analysis Set: Received Study Drug |
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| COMPLETED |
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| NOT COMPLETED |
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| Down-Titration Period |
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Safety Analysis Set (SAS) included all randomized participants who took at least one dose of study medication. Main Treatment Period.
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| ID | Title | Description |
|---|---|---|
| BG000 | Roflumilast 250 μg OD Then 500 μg OD | Roflumilast 250 μg, tablets, orally, once daily (OD) for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks in the Main Treatment Period. Any participants not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. |
| BG001 | Roflumilast 500 μg EOD Then 500 μg OD | Roflumilast 500 μg, tablets, orally, every other day (EOD), and roflumilast placebo-matching tablets, orally, every other day on non-treatment days, for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks in the Main Treatment Period. Any participants not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. |
| BG002 | Roflumilast 500 μg OD | Roflumilast 500 μg, tablets, orally, once daily (OD) at least 1 dose in the Main Period. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Number | participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Region of Enrollment | Number | participants |
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| Height | Mean | Standard Deviation | cm |
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| Weight | Mean | Standard Deviation | kg |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
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| Smoking Classification | Number | participants |
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| Number of Cigarette Pack-Years | Number of pack-years = (number of cigarettes smoked per day/20) × number of years smoked | Mean | Standard Deviation | pack-years |
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| Pre-bronchodilator Forced Expiratory Volume in the First Second (FEV1) | Mean | Standard Deviation | liters |
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| Pre-Bronchodilator Forced Vital Capacity (FVC) | Mean | Standard Deviation | liters |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Percentage of Participants Prematurely Discontinuing Study Treatment Due to Any Reason | The primary endpoint is the percentage of participants prematurely discontinuing study treatment for any reason during the Main Period from Visit 1 (V1) to Last Visit (Vend). Discontinuation is defined as permanently stopping randomized treatment; participants who resume randomized treatment after an interval will not be counted as having discontinued. The analysis used discontinuations occurring during the Main Period, irrespective of whether a participant subsequently entered into the Down-Titration Period. | Safety Analysis Set (SAS) included all randomized participants who took at least one dose of study medication. | Posted | Number | percentage of participants | Baseline to Week 12 (Main Period) |
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| Secondary | Percentage of Participants With Adverse Events of Interest | Adverse events of interest to evaluate tolerability are defined as diarrhea, nausea, headache, decreased appetite, insomnia and abdominal pain. | SAS included all randomized participants who took at least one dose of study medication. | Posted | Number | percentage of participants | Baseline to Week 12 (Main Period) |
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| Secondary | Change From Baseline (V0DT) in Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) to Final Visit of the Down-Titration Period | 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 prior to taking study medication A positive change from Baseline indicates improvement. | Participants from the Down-Titration Period Full Analysis Set (FAS), all randomized participants who entered this period, regardless of whether they took study medication, with data available for analysis. | Posted | Mean | Standard Deviation | Liters | Baseline (V0DT) [assessment at end of main period] and Final Visit of Down-Titration Period (Up to Day 56) |
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| Secondary | Percentage of Participants Prematurely Discontinuing Study Treatment Due to Any Reason During Down-Titration Period | Down-Titration Period Full Analysis Set (FAS) included all randomized participants who entered this period, regardless of whether they took study medication. | Posted | Number | percentage of participants | Baseline DT (Day 1 of Down-Titration Period) to Week 8 (Down-Titration Period) |
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| Secondary | Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) During the Down-Titration Period | 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 prior to taking study medication. A positive change from Baseline indicates improvement. | Down-Titration Period Full Analysis Set (FAS) included all randomized participants who entered this period, regardless of whether they took study medication. "n" in each category is the number of participants with data available at the given time-point. | Posted | Mean | Standard Deviation | Liters | Baseline DT (Day 1 of Down-Titration Period) to Days 14, 28 and 56 (Down-Titration Period) |
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| Secondary | Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) During the Main Period | 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 prior to taking study medication. A positive change from Baseline indicates improvement. | Main Period FAS included all randomized participants, regardless of whether they took study medication. "n" in each of the categories is the number of participants with data available at the given time-point. | Posted | Mean | Standard Deviation | Liters | Baseline (Day 1 of Main Period) to Days 15, 29, 57 and 84 (Main Period) |
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| Secondary | Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) During the Main Period | 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 prior to taking study medication. A positive change from Baseline indicates improvement. | Main Period FAS included all randomized participants, regardless of whether they took study medication. "n" in each of the categories is the number of participants with data available at the given time-point. | Posted | Mean | Standard Deviation | Liters | Baseline (Day 1 of Main Period) to Days 15, 29, 57 and 84 (Main Period) |
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| Secondary | Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) During the Down-Titration Period | 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 prior to taking study medication. A positive change from Baseline indicates improvement. | Down-Titration Period Full Analysis Set (FAS) included all randomized participants who entered this period, regardless of whether they took study medication. | Posted | Mean | Standard Deviation | Liters | Baseline DT (Day 1 of Down-Titration Period) to Days 14, 28 and 56 (Down-Titration Period) |
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| Secondary | Change From Baseline in Treatment Satisfaction Scores During the Main Period | Participants will be asked to assess their satisfaction with their COPD therapy at each visit. The participants will rate their treatment satisfaction on a 7-point scale where 0=very satisfied, 1=satisfied, 2=somewhat satisfied, 3=neither satisfied nor dissatisfied, 4=somewhat dissatisfied, 5=dissatisfied and 6=very dissatisfied. A negative change from Baseline indicates improvement. | Main Period FAS included all randomized participants, regardless of whether they took study medication. "n" in each of the categories is the number of participants with data available at the given time-point. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 1 of Main Period) to Days 15, 29, 57 and 84 (Main Period) |
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| Secondary | Change From Baseline in Treatment Satisfaction Scores During the Down-Titration Period | Participants will be asked to assess their satisfaction with their COPD therapy at each visit. The participants will rate their treatment satisfaction on a 7-point scale where 0=very satisfied, 1=satisfied, 2=somewhat satisfied, 3=neither satisfied nor dissatisfied, 4=somewhat dissatisfied, 5=dissatisfied and 6=very dissatisfied. A negative change from Baseline indicates improvement. | Down-Titration Period Full Analysis Set (FAS) included all randomized participants who entered this period, regardless of whether they took study medication. "n" in each of the categories is the number of participants with data available at the given time-point. | Posted | Mean | Standard Deviation | score on a scale | Baseline DT (Day 1 of Down-Titration Period) to Days 14, 28 and 56 (Down-Titration Period) |
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| Secondary | Population PK Model Point Estimate for Absorption Rate Constant (Ka) of Roflumilast and Roflumilast N-oxide | PK model point estimates for Ka are calculated using all available PK data for all doses of roflumilast combined and are presented for roflumilast and metabolite roflumilast N-oxide. Results are reported for the subgroups defined according to the covariates (weight, age, smoking status and sex) included in the final model. | Pharmacokinetic (PK) Set included all participants who had at least 1 quantifiable PK concentration. | Posted | Number | units per hour (1/h) | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours at weeks 2 or 8 |
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| Secondary | Population PK Model Point Estimate for Apparent Oral Clearance (CL/F) of Roflumilast and Roflumilast N-oxide | PK model point estimates for CL/F are calculated using all available PK data for all doses of roflumilast combined and are presented for roflumilast and metabolite roflumilast N-oxide. Results are reported for the subgroups defined according to the covariates (weight, age, smoking status and sex) included in the final model. | Pharmacokinetic (PK) Set included all participants who had at least 1 quantifiable PK concentration. | Posted | Number | liters per hour (L/h) | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours at weeks 2 or 8 |
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| Secondary | Population PK Model Point Estimate for Apparent Central Volume (Vc/F) of Roflumilast and Roflumilast N-oxide | PK model point estimates for Vc/F are calculated using all available PK data for all doses of roflumilast combined and are presented for roflumilast and metabolite roflumilast N-oxide. Results are reported for the subgroups defined according to the covariates (weight, age, smoking status and sex) included in the final model. | Pharmacokinetic (PK) Set included all participants who had at least 1 quantifiable PK concentration. | Posted | Number | liters (L) | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours at weeks 2 or 8 |
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| Secondary | Population PK Model Point Estimate for Apparent Peripheral Volume (Vp/F) of Roflumilast and Roflumilast N-oxide | PK model point estimates for Vp/F are calculated using all available PK data for all doses of roflumilast combined and are presented for roflumilast and metabolite roflumilast N-oxide. Results are reported for the subgroups defined according to the covariates (weight, age, smoking status and sex) included in the final model. | Pharmacokinetic (PK) Set included all participants who had at least 1 quantifiable PK concentration. | Posted | Number | L | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours at weeks 2 or 8 |
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| Secondary | Total PDE4 Inhibitory Activity (tPDE4i) | tPDE4i was derived using in-vitro constants for protein binding and biochemical activity (IC50). tPDE4i is reported for a set of reference participants defined according to the covariates included in the final model. | Participants from the PK Set, all participants who had at least 1 quantifiable PK concentration, with data available. Study design only includes the 250 µg arm for analyses of this outcome measure in the Down-Titration period. Measured values are predicted values reported as median and 90% prediction interval. | Posted | Median | 90% Confidence Interval | unitless | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours post-dose at Days 15 and 57. Down-titration: Pre-dose and 1,2,3,4,6 hours post-dose at Days 1 and 14 and pre-dose at Days 28 and 56. |
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| Secondary | Summary Statistics of Predicted Total PDE4 Inhibitory Activity (tPDE4i) | tPDE4i was derived using in-vitro constants for protein binding and biochemical activity (IC50). An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. Adverse Events of Interest (AEI) for PK analyses included: headache, diarrhea, nausea, vomiting, abdominal pain, appetite disorders, sleep disorders, angioedema, psychiatric disorders (anxiety, nervousness), psychiatric disorders (depression,suicidal ideation,behaviour) and weight loss. | PK Set included all participants who had at least 1 quantifiable PK concentration. "n" in the category is the number of participants with available data. Study design only includes the 250 µg OD and 500 µg OD arms for analyses of this outcome measure. Measured values are predicted values reported as median and 90% prediction interval. | Posted | Median | 90% Confidence Interval | unitless | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours post-dose at Days 15 and 57. Down-titration: Pre-dose and 1,2,3,4,6 hours post-dose at Days 1 and 14 and pre-dose at Days 28 and 56. |
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| Secondary | Median Simulated Percentage of Participants With Adverse Events of Interest | The PK model predicted the total PDE4 inhibitory activity and the median simulated percentage of participants with Adverse Events of Interest during 12 weeks of treatment based on 1000 participants simulated. Results are reported for the set of reference participants defined according to the covariates [weight, smoking status, sex, age and long acting muscarinic antagonist (LAMA)] included in the final model and tPDE4i. Adverse Events of Interest (AEI) for PK analyses included: headache, diarrhea, nausea, vomiting, abdominal pain, appetite disorders, sleep disorders, angioedema, psychiatric disorders (anxiety, nervousness), psychiatric disorders (depression, suicidal ideation, behaviour) and weight loss. | Pharmacokinetic (PK) Set included all participants who had at least 1 quantifiable PK concentration. Number of participants analyzed is the number of participants simulated. Measured values are predicted values. | Posted | Number | percentage of participants | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours post-dose at Days 15 and 57. AEIs: 12 Weeks |
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| Secondary | Median Simulated Absolute Change From Baseline in FEV1 at Weeks 4 and 12 | The PK model predicted the total PDE4 inhibitory activity and the median simulated Change from Baseline (CFB) in FEV1 at Week 4 and the Change from Baseline in FEV1 at Week 12 during 12 weeks of treatment with roflumilast 500 μg OD based on 1000 participants simulated. Results are reported for the set of reference participants defined according to the covariates [weight, smoking status, sex, age, race, COPD severity, concomitant long acting muscarinic antagonist (LAMA) and Percent FEV1 reversibility] included in the final model and tPDE4i. 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 prior to taking study medication. A positive change from Baseline indicates improvement. | Pharmacokinetic (PK) Set included all participants who had at least 1 quantifiable PK concentration. The number of participants analyzed is the number of participants simulated. Measured values are predicted values. | Posted | Number | milliliters (mL) | Main period: Pre-dose and 1,2,3,4,6 hours post-dose or pre-dose and 2 hours post-dose at Days 15 and 57. FEV-1: Pre-dose and Weeks 4 and 12 |
|
Main Treatment Period: First dose of study drug to 30 days past last dose or first dose in the Down-Titration Period (Up to 114 Days). Down-Titration Period: First dose of study drug to 30 days past the last dose of study drug (Up to 86 Days).
Due to the design of the study, the most common (≥ 2%) non-serious adverse events were determined separately for each period, the blinded Main Treatment Period and the open-label Down-Titration Period. A result of 0 means that the event did not meet the ≥ 2% threshold for that study period but did meet the threshold for the other study period.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Roflumilast 250 μg OD Then 500 μg OD_Main Treatment Period | Roflumilast 250 μg, tablets, orally, once daily (OD) for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks in the Main Treatment Period. Any participants not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. | 19 | 441 | 239 | 441 | ||
| EG001 | Roflumilast 500 μg EOD Then 500 μg OD_Main Treatment Period | Roflumilast 500 μg, tablets, orally, every other day (EOD), and roflumilast placebo-matching tablets, orally, every other day on non-treatment days, for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks in the Main Treatment Period. Any participants not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. | 22 | 437 | 248 | 437 | ||
| EG002 | Roflumilast 500 μg OD_Main Treatment Period | Roflumilast 500 μg tablets, orally, once daily for 12 weeks in the Main Treatment Period. Any participants not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. | 20 | 443 | 272 | 443 | ||
| EG003 | Roflumilast 250 μg OD Then 500 μg OD_Down Titration Period | Participants in the roflumilast 250 μg once daily (OD) then 500 μg OD who were not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. | 1 | 27 | 13 | 27 | ||
| EG004 | Roflumilast 500 μg EOD_Down-Titration Period | Participants in the roflumilast 500 μg, every other day (EOD) treatment arm who were not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. | 0 | 39 | 21 | 39 | ||
| EG005 | Roflumilast 500 μg OD_Down Titration Period | Participants in the roflumilast 500 μg once daily (OD) treatment arm who were not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. | 0 | 38 | 25 | 38 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myocardial infarction | Cardiac disorders | MedDRA 18.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with roflumilast 500 μg OD and is not related (previous AE included severe syncope). |
|
| Myocardial ischaemia | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 18.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with roflumilast 250 μg OD then 500 μg OD and is not related (previous AE included moderate COPD). |
|
| Cardiopulmonary failure | Cardiac disorders | MedDRA 18.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with roflumilast 250 μg OD then 500 μg OD and is not related (previous AE included moderate COPD). |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Abdominal mass | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Colitis ulcerative | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Femoral hernia incarcerated | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Infective exacerbation of chronic obstructive airways disease | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Acute sinusitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Bronchopneumonia | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Lung adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with roflumilast 500 μg OD and is not related (previous AE included concurrent moderate haemoptysis). |
|
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Transitional cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with roflumilast 250 μg OD then 500 μg OD and is not related (previous AE included concurrent moderate pneumonia). |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Pneumothorax spontaneous | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with roflumilast 500 µg EOD then 500 µg OD and is not related. |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hypertensive crisis | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Vasculitis | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Chalazion | Eye disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Bowel movement irregularity | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Duodenitis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Feeling hot | General disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Viral pharyngitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Procedural dizziness | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Postmenopausal haemorrhage | Reproductive system and breast disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| AstraZeneca Clinical Study Information Center | AstraZeneca | 1-877-240-9479 | information.center@astrazeneca.com |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C424423 | Roflumilast |
Not provided
Not provided
Not provided
| Reason Not Specified |
|
| 65-84 years |
|
| 85 years and over |
|
| Male |
|
| Not Hispanic or Latino |
|
| Missing |
|
| Asian |
|
| Black or African American |
|
| Native Hawaiian/Other Pacific Islander |
|
| White |
|
| Germany |
|
| Greece |
|
| Hungary |
|
| Korea, Republic Of |
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| Philippines |
|
| Poland |
|
| Romania |
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| Russia |
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| Slovakia |
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| South Africa |
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| Spain |
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| Thailand |
|
| Ukraine |
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| United Kingdom |
|
| Ex-smoker |
|
Analyses were performed using a hierarchical testing procedure. |
| Cox Proportional Hazard |
| 0.68 |
| 2-Sided |
| 95 |
| 0.51 |
| 0.92 |
Cox proportional hazards model with study treatment and country as class effects, and baseline FEV1 as a continuous variable. |
| Superiority or Other |
| Analyses were performed using a hierarchical testing procedure. | Regression, Logistic | 0.114 | Study treatment, country and baseline forced expiratory volume in the first second (FEV1) as explanatory variables. | Odds Ratio (OR) | 0.76 | 2-Sided | 95 | 0.55 | 1.07 | Superiority or Other |
| Analyses were performed using a hierarchical testing procedure. | Cox Proportional Hazard | 0.77 | 2-Sided | 95 | 0.58 | 1.02 | Cox proportional hazards model with study treatment and country as class effects, and baseline FEV1 as a continuous variable. | Superiority or Other |
| Roflumilast 500 μg OD |
Roflumilast 500 μg, tablets, orally, once daily (OD) at least 1 dose in the Main Period. |
|
|
|
| OG002 | Roflumilast 500 μg OD_Down Titration Period | Participants in the roflumilast 500 μg once daily (OD) treatment arm who were not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. |
|
|
|
|
| OG002 | Roflumilast 500 μg OD_Down Titration Period | Participants in the roflumilast 500 μg once daily (OD) treatment arm who were not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. |
|
|
| OG002 | Roflumilast 500 μg OD | Roflumilast 500 μg, tablets, orally, once daily (OD) at least 1 dose in the Main Period. |
|
|
| OG002 | Roflumilast 500 μg OD | Roflumilast 500 μg, tablets, orally, once daily (OD) at least 1 dose in the Main Period. |
|
|
| Roflumilast 500 μg OD_Down Titration Period |
Participants in the roflumilast 500 μg once daily (OD) treatment arm who were not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. |
|
|
| OG002 | Roflumilast 500 μg OD | Roflumilast 500 μg, tablets, orally, once daily (OD) at least 1 dose in the Main Period. |
|
|
| OG002 | Roflumilast 500 μg OD_Down Titration Period | Participants in the roflumilast 500 μg once daily (OD) treatment arm who were not tolerating study treatment were prematurely discontinued and received roflumilast 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. |
|
|
|
|
|
|
| OG003 | Roflumilast 250 µg Down-Titration | 250 μg, tablets, orally, once daily for 8 weeks in the open-label Down-Titration Period. |
|
|
Roflumilast 500 μg at least one dose in the Main Period followed by Roflumilast 250 μg tablets, orally, once daily in the Down -Titration Period. |
|
|
| OG002 | Roflumilast 500 μg OD | Roflumilast 500 μg, tablets, orally, once daily (OD) at least 1 dose in the Main Period. |
|
|
Roflumilast 500 μg, tablets, orally, once daily (OD) for 12 weeks. Results for Change from Baseline in FEV1 at Week 12. |
|
|