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Roflumilast in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Fixed Combinations of Long-acting β2-agonists (LABA) and Inhaled Glucocorticosteroid (ICS) (REACT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01329029
First received: March 30, 2011
Last updated: September 25, 2015
Last verified: September 2015
  Purpose

The objective of the REACT trial is to investigate the effect of roflumilast 500 μg tablets once daily versus placebo on exacerbation rate and pulmonary function in COPD patients who are concomitantly treated with a fixed combination of long-acting β2-agonists (LABA) and inhaled glucocorticosteroids (ICS). In addition, data on safety and tolerability of roflumilast will be obtained. An additional objective is to further characterize the population pharmacokinetic profile of roflumilast and roflumilast N oxide and to further characterize their pharmacokinetics/pharmacodynamics (PK/PD) relationship in terms of efficacy and relevant safety aspects.

Patients to be included are required to have severe COPD associated with chronic bronchitis and a history of frequent exacerbations and must be concomitantly treated with a fixed combination of LABA and ICS. Two parallel treatment arms (roflumilast 500 μg once daily and placebo) are included.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: Roflumilast
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Roflumilast on Exacerbation Rate in Patients With COPD Treated With Fixed Combinations of LABA and ICS. A 52-week, Randomised Double-blind Trial With Roflumilast 500 µg Versus Placebo. The REACT Trial

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Rate of Moderate or Severe COPD Exacerbations Per Patient Per Year [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    A COPD exacerbation is an event in the natural course of the disease characterized by a worsening in the patient's baseline dyspnoea, cough, and/or sputum production beyond day to day variability sufficient to warrant a change in management. COPD exacerbations were categorized as follows: Severe=Requiring hospitalization and/or leading to death; Moderate=Requiring oral or parenteral glucocorticosteroid therapy. The defined number of days a patient was in the trial was divided by 365.25, in order to express the duration as a fraction of 1 year.


Secondary Outcome Measures:
  • Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in the First Second (FEV1) [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Pulmonary function testing was performed using centralised spirometry. FEV1 is the maximum amount of air that can be forcefully exhaled in one second. Least-squares means is from Analysis of Covariance (ANCOVA) including treatment by time interaction. A positive change from Baseline indicates improvement.

  • Rate of Severe COPD Exacerbations Per Patient Per Year [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    A COPD exacerbation is an event in the natural course of the disease characterized by a worsening in the patient's baseline dyspnoea, cough, and/or sputum production beyond day to day variability sufficient to warrant a change in management. Severe COPD exacerbations were categorized as requiring hospitalization and/or leading to death. The defined number of days a patient was in the trial was divided by 365.25, in order to express the duration as a fraction of 1 year.

  • Rate of COPD Exacerbations Per Patient Per Year All Categories [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    A COPD exacerbation is an event in the natural course of the disease characterized by a worsening in the patient's baseline dyspnoea, cough, and/or sputum production beyond day to day variability sufficient to warrant a change in management. COPD exacerbations were categorized as follows: Severe=Requiring hospitalization and/or leading to death; Moderate=Requiring oral or parenteral glucocorticosteroid therapy. The defined number of days a patient was in the trial was divided by 365.25, in order to express the duration as a fraction of 1 year.

  • Percentage of Participants Experiencing at Least 1 COPD Exacerbation [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    A COPD exacerbation is an event in the natural course of the disease characterized by a worsening in the patient's baseline dyspnoea, cough, and/or sputum production beyond day to day variability sufficient to warrant a change in management.

  • Time to First COPD Exacerbation All Categories [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    Time to event was calculated as date of onset of event — date of first intake of double-blind study drug + 1 day for all events: mild, moderate or severe. A COPD exacerbation is an event in the natural course of the disease characterized by a worsening in the patient's baseline dyspnoea, cough, and/or sputum production beyond day to day variability sufficient to warrant a change in management.

  • Time to Second Moderate or Severe COPD Exacerbation [ Time Frame: 52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis) ] [ Designated as safety issue: No ]
    Time to event was calculated as date of onset of event — date of first intake of double-blind study drug + 1 day for events: moderate or severe. A COPD exacerbation is an event in the natural course of the disease characterized by a worsening in the patient's baseline dyspnoea, cough, and/or sputum production beyond day to day variability sufficient to warrant a change in management. COPD exacerbations were categorized as Severe: Requiring hospitalization and/or leading to death; Moderate: Requiring oral or parenteral glucocorticosteroid therapy.

  • Time to Third Moderate or Severe COPD Exacerbation [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    Time to event was calculated as date of onset of event — date of first intake of double-blind study drug + 1 day for events: moderate or severe. A COPD exacerbation is an event in the natural course of the disease characterized by a worsening in the patient's baseline dyspnoea, cough, and/or sputum production beyond day to day variability sufficient to warrant a change in management. COPD exacerbations were categorized as Severe: Requiring hospitalization and/or leading to death; Moderate: Requiring oral or parenteral glucocorticosteroid therapy.

  • Number of Patients Needed to Treat to Avoid 1 Moderate or Severe COPD Exacerbation Derived From Exacerbation Per Patient Per Year [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    The number needed to treat (NNT) analysis is a simple, concise method to quantify directly the benefits that alternative treatment options have on disease outcomes in terms of the number of patients who need to be treated before a benefit is observed. Risk reduction: Rate(Placebo)— Rate (Roflumilast 500 μg), Number needed to treat for benefit (NNTB): 1/(Risk reduction). A COPD exacerbation is an event in the natural course of the disease characterized by a worsening in the patient's baseline dyspnoea, cough, and/or sputum production beyond day to day variability sufficient to warrant a change in management. COPD exacerbations were categorized as Severe: Requiring hospitalization and/or leading to death; Moderate: Requiring oral or parenteral glucocorticosteroid therapy.

  • Number of Moderate or Severe COPD Exacerbation Days [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    A COPD exacerbation is an event in the natural course of the disease characterized by a worsening in the patient's baseline dyspnoea, cough, and/or sputum production beyond day to day variability sufficient to warrant a change in management. The number of exacerbation days per patient is the sum of durations (stop date of exacerbation — start date of exacerbation + 1) of all exacerbations within the category.

  • Duration of Moderate or Severe COPD Exacerbations Per Participant [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    A COPD exacerbation is an event in the natural course of the disease characterized by a worsening in the patient's baseline dyspnoea, cough, and/or sputum production beyond day to day variability sufficient to warrant a change in management.

  • Change From Baseline in Post-Bronchodilator Forced Vital Capacity (FVC) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Forced vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Least-squares means was from ANCOVA including treatment by time interaction. A positive change from Baseline indicates improvement.

  • Change From Baseline in Post-Bronchodilator Forced Expiratory Flow at 25% to 75% of Vital Capacity (FEF25-75%) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Forced expiratory flow 25-75% (FEF25-75%) is the flow (or speed) of air coming out of the lung during the middle half of a forced expiration. Pulmonary function testing was performed using centralized spirometry. Least-squares means was from ANCOVA including treatment by time interaction. A positive change from Baseline indicates improvement.

  • Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in the First 6 Seconds (FEV6) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    FEV6 is the amount of air which can be forcibly exhaled from the lungs in the first six seconds of a forced exhalation. Pulmonary function testing was performed using centralized spirometry. A positive change from Baseline indicates improvement.

  • Change From Baseline in Post-Bronchodilator FEV1/FVC [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    The FEV1/FVC ratio represents the percentage of vital capacity expelled from the lungs during the first second of a forced exhalation. Pulmonary function testing was performed using centralized spirometry. A positive change from Baseline indicates improvement.

  • Change From Baseline in Use of Rescue Medication From Daily Diary [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Salbutamol metered dose inhaler was available as rescue medication during the study. The participant recorded the use of rescue medication in a daily diary. A negative change from Baseline indicates an improvement.

  • Change From Baseline in COPD Symptom Score From Daily Diary [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Participants recorded COPD symptoms cough and sputum production in a daily diary. Cough was assessed using a 4-point scale where 0=No cough to 3=severe cough and sputum was assessed using a 4-point scale where 0=no sputum production to 3=severe sputum production. Least-squares means from ANCOVA including treatment by time interaction. A negative change from Baseline indicates improvement. Total symptom score is the sum of cough and sputum scores, ranging from 0 (best possible outcome) to 6 (worst possible outcome).

  • Percentage of Symptom-Free Days [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    Symptoms of COPD (cough, sputum) were recorded in a daily diary. The percentage of days without symptoms is reported.

  • Percentage of Rescue Medication-Free Days [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    Participants recorded their use of rescue medication in a daily diary. The percentage of days without rescue medication use.

  • Change From Baseline in COPD Assessment Test (CAT) Total Score [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Participants completed the CAT questionnaire at Baseline and after 52 Weeks of Treatment. The CAT questionnaire measures the impact of COPD on wellbeing and daily life. Participants answer 8 questions on a scale from 0 (best) to 5 (worst). The total score ranges from 0 to 40 with higher scores indicating more impact. A negative change from Baseline indicates improvement. Least-squares means from ANCOVA including treatment by time interaction.

  • Percentage of Participants With Improvement in CAT [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Participants completed the CAT questionnaire at Baseline and after 52 Weeks of treatment. The CAT questionnaire measures the impact of COPD on wellbeing and daily life. Participants answer 8 questions on a scale from 0 (best) to 5 (worst). The total score ranges from 0 to 40 with higher scores indicating more impact. Improvement was defined as a CAT Total Score reduction from Baseline > 1.6.

  • Time to Mortality Due to Any Reason During the Treatment Period Score [ Time Frame: 52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis) ] [ Designated as safety issue: No ]
    Time to event will be calculated as date of onset of event — date of first intake of double-blind study drug + 1 day.

  • Time to Mortality Due to COPD Exacerbation During the Treatment Period [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    Time to event will be calculated as date of onset of event — date of first intake of double-blind study drug + 1 day.

  • Time to Withdrawal During the Treatment Period [ Time Frame: 52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis) ] [ Designated as safety issue: No ]
    Time to event will be calculated as date of onset of event — date of first intake of double-blind study drug + 1 day.

  • Time to Withdrawal Due to COPD Exacerbation During the Treatment Period [ Time Frame: 52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis) ] [ Designated as safety issue: No ]
    Time to event will be calculated as date of onset of event — date of first intake of double-blind study drug + 1 day.

  • Percentage of Participants With Major Adverse Cardiovascular Event (MACE) During the Treatment Period [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    Composite MACE is a combined endpoint (cardiovascular death [including death due to undetermined cause], nonfatal myocardial infarction, and nonfatal stroke).

  • Time to First Major Adverse Cardiovascular Event (MACE) During the Treatment Period [ Time Frame: 52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis) ] [ Designated as safety issue: No ]
    Composite MACE is a combined endpoint(cardiovascular death [including death due to undetermined cause], nonfatal myocardial infarction, and nonfatal stroke). Time to event was calculated as date of onset of event — date of first intake of double-blind study drug + 1 day.

  • Percentage of Participant With All-Cause Hospitalisation During the Treatment Period [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    Percentage of patients with at least one hospital admission due to any cause.

  • Time to First Hospitalisation Due to Any Cause During the Treatment Period [ Time Frame: 52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis) ] [ Designated as safety issue: No ]
    Time to event will be calculated as date of onset of event — date of first intake of double-blind study drug + 1 day.

  • Time to Trial Withdrawal Due to an Adverse Event [ Time Frame: 52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis) ] [ Designated as safety issue: No ]
    Time to event will be calculated as date of onset of event — date of first intake of double-blind study drug + 1 day.

  • Percentage of Participants Who Experienced at Least 1 Treatment Emergent Adverse Event (TEAE) [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]
    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. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

  • Change From Baseline in Body Weight [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: Yes ]
    Least Square Means was from an ANCOVA model including Last Observation Carried Forward (LOCF).

  • Change From Baseline in Body Mass Index (BMI) [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: Yes ]
    Body mass index (BMI) is a measure of body fat based on height and weight. Least Square Means was from an ANCOVA model including LOCF.


Enrollment: 1945
Study Start Date: May 2011
Study Completion Date: May 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Roflumilast
concomitant medication: fixed combination of long-acting β2-agonist and inhaled glucocorticosteroid
Drug: Roflumilast
500 µg, once daily
Placebo Comparator: Placebo
concomitant medication: fixed combination of long-acting β2-agonist and inhaled glucocorticosteroid
Drug: Placebo
once daily

Detailed Description:

The drug tested in this study is called Roflumilast. Roflumilast is being developed to treat people who have chronic obstructive pulmonary disease (COPD). This study investigated the effect of roflumilast 500 μg tablets once daily versus placebo on exacerbation rate, pulmonary function, and major adverse cardiovascular events (MACE) in COPD patients who were concomitantly treated with a fixed combination of long-acting beta-agonists (LABA) and inhaled glucocorticosteroids.

The study was targeted to enroll approximately 1934 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups—which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):

  • Roflumilast 500 μg once daily
  • Placebo (dummy inactive pill) - this was a tablet that looked like the study drug but had no active ingredient

Trial treatment was taken in the morning by mouth after breakfast with some water.

The trial consisted of the following periods:

  • Single-blind baseline period (4 weeks) during which all patients received placebo.
  • Double-blind treatment period (52 weeks) during which patients received either roflumilast or matching placebo.
  • Safety follow-up (30 days after end of treatment (Vend) or premature discontinuation date) in case of ongoing Adverse Events at Vend, if necessary.
  • Follow-up visit 12 weeks after end of treatment, at Week 64 (VFU), only for patients who completed the trial as scheduled.

This multi-center trial was conducted worldwide. The overall time to participate in this study was up to 64 weeks. Participants made multiple visits to the clinic which included a follow-up visit at week 64.

  Eligibility

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

Inclusion Criteria:

  • Giving written informed consent
  • History of COPD (according to GOLD 2009) for at least 12 months prior to baseline Visit V0 associated with chronic productive cough for 3 months in each of the 2 years prior to baseline visit (with other causes of productive cough excluded)
  • Age ≥ 40 years
  • Forced expiratory volume after one second (FEV1)/forced vital capacity (FVC) ratio (post-bronchodilator) < 70%
  • FEV1 (post-bronchodilator) ≤ 50% of predicted
  • At least two documented moderate or severe COPD exacerbations within one year prior to baseline visit
  • Patients must be pre-treated with LABA and ICS for at least 12 months before baseline Visit V0. Up to 3 months before baseline Visit V0 free or fixed combinations of LABA and ICS are allowed, including changes in dose, active substances, and brands. In the last 3 months before baseline Visit V0 patients must be pre-treated with fixed combinations of LABA and ICS at a constant dose (maximum approved dosage strength of the combination).
  • Former smoker (defined as smoking cessation at least one year ago) or current smoker both with a smoking history of at least 20 pack years

Main Exclusion Criteria:

  • Exacerbations not resolved at first baseline visit
  • Diagnosis of asthma and/or other relevant lung disease
  • Known alpha-1-antitrypsin deficiency
  • Other protocol-defined exclusion criteria may apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01329029

  Hide Study Locations
Locations
Australia
Nycomed Investigational Site
Box Hill, Australia, 3128
Nycomed Investigational Site
Clayton, Australia, 3168
Nycomed Investigational Site
Concord, Australia, 2139
Nycomed Investigational site
Daws Park, Australia, 5041
Nycomed Investigational Site
Frankston, Australia, 3199
Nycomed Investigational Site
Heidelberg, Australia, 3084
Nycomed Investigational Site
Parkville, Australia, 3050
Nycomed Investigational Site
Toorak Gardens, Australia, 5065
Austria
Nycomed Investigational Site
Feldbach, Austria, 8330
Nycomed Investigational Site
Graz, Austria, 8036
Nycomed Investigational Site
Salzburg, Austria, 5020
Nycomed Investigational Site
Wien, Austria, 1140
Belgium
Nycomed Investigational Site
Bruxelles, Belgium, 1000
Nycomed Investigational Site
Bruxelles, Belgium, 1200
Nycomed Investigational Site
Halen, Belgium, 3545
Nycomed Investigational Site
Liege, Belgium, 4000
Nycomed Investigational Site
Malmedy, Belgium, 4960
Brazil
Nycomed Investigational Site
Belo Horizonte, Brazil
Nycomed Investigational Site
Botucatu, Brazil
Nycomed Investigational Site
Florianópolis, Brazil
Nycomed Investigational Site
Goiânia, Brazil
Nycomed Investigational Site
Porto Alegre, Brazil
Nycomed Investigational Site
Rio de Janeiro, Brazil
Nycomed Investigational Site
Sao Paolo, Brazil
Nycomed Investigational Site
Vitória, Brazil
Canada
Nycomed Investigational Site
Hamilton, Canada, L8N 4A6
Nycomed Investigational Site
Kingston, Canada, K7L 2V7
Nycomed Investigational Site
Lachine, Canada, H8S 2E4
Nycomed Investigational Site
Niagara Falls, Canada, L2G 1J4
Nycomed Investigational Site
Richmond Hill, Canada, L4C 2N9
Nycomed Investigational Site
Toronto, Canada, M5T 3A9
Nycomed Investigational Site
Toronto, Canada, M6H 3M2
Nycomed Investigational Site
Winnepeg, Canada, R2K 3S8
Denmark
Nycomed Investigational Site
Hellerup, Denmark, 2900
Nycomed Investigational Site
Hillerød, Denmark, 3400
Nycomed Investigational Site
Hvidovre, Denmark, 2650
Nycomed Investigational Site
København NV, Denmark, 2400
France
Nycomed Investigational Site
Férolles Attilly, France, 77150
Nycomed Investigational Site
Nîmes, France, 30900
Nycomed Investigational Site
Poitiers, France, 86021
Nycomed Investigational Site
Saint-Laurent du Var, France, 06700
Nycomed Investigational Site
Strasbourg, France, 67091
Germany
Nycomed Investigational Site
Berlin, Germany, 10367
Nycomed Investigational Site
Berlin, Germany, 10969
Nycomed Investigational Site
Berlin, Germany, 12203
Nycomed Investigational Site
Fürth, Germany, 90766
Nycomed Investigational Site
Großhansdorf, Germany, 22927
Nycomed Investigational Site
Hannover, Germany, 30167
Nycomed Investigational Site
Homburg, Germany, 66421
Nycomed Investigational Site
Koblenz, Germany, 56068
Nycomed Investigational Site
Marburg, Germany, 35043
Nycomed Investigational Site
Rüdersdorf, Germany, 15562
Greece
Nycomed Investigational Site
Alexandroupolis, Greece, 68100
Nycomed Investigational Site
Athens, Greece, 10676
Nycomed Investigational Site
Athens, Greece, 11527
Nycomed Investigational Site
Heraklion, Crete, Greece, 71110
Nycomed Investigational Site
Kavala, Greece, 65201
Nycomed Investigational Site
Larissa, Greece, 41100
Nycomed Investigational Site
Marousi, Greece, 15126
Nycomed Investigational Site
Thessaloniki, Greece, 57010
Hungary
Nycomed Investigational Site
Balassagyarmat, Hungary, 2660
Nycomed Investigational Site
Budapest, Hungary, 1125
Nycomed Investigational Site
Cegléd, Hungary, 2700
Nycomed Investigational Site
Csorna, Hungary, 9300
Nycomed Investigational Site
Deszk, Hungary, 6772
Nycomed Investigational Site
Erd, Hungary
Nycomed Investigational Site
Miskolc, Hungary, 3526
Nycomed Investigational Site
Nyíregyháza, Hungary, 4400
Nycomed Investigational Site
Pécs, Hungary, 7623
Nycomed Investigational Site
Siófok, Hungary, 8600
Nycomed Investigational Site
Sopron, Hungary, 9400
Nycomed Investigational Site
Szombathely, Hungary, 9700
Nycomed Investigational Site
Törökbálint, Hungary, 2045
Israel
Nycomed Investigational Site
Ashkelon, Israel, 78278
Nycomed Investigational Site
Beer Sheva, Israel, 84101
Nycomed Investigational Site
Haifa, Israel, 31096
Nycomed Investigational Site
Haifa, Israel, 34362
Nycomed Investigational Site
Holon, Israel, 58100
Nycomed Investigational Site
Jerusalem, Israel, 91031
Nycomed Investigational Site
Jerusalm, Israel, 91120
Nycomed Investigational Site
Kfar Saba, Israel, 44281
Nycomed Investigational Site
Petach Tikva, Israel, 49100
Nycomed Investigational Site
Rehovot, Israel, 76100
Nycomed Investigational Site
Tel Aviv, Israel, 67891
Nycomed Investigational Site
Tel Hashomer, Israel, 52621
Nycomed Investigational Site
Tel-Aviv, Israel, 64239
Italy
Nycomed Investigational Site
Ferrara, Italy, 44011
Nycomed Investigational Site
Genova, Italy, 16132
Nycomed Investigational Site
Milano, Italy, 20122
Nycomed Investigational Site
Milano, Italy, 20138
Nycomed Investigational Site
Modena, Italy, 41100
Nycomed Investigational Site
Monza, Italy, 20052
Nycomed Investigational Site
Pordenone, Italy, 33170
Nycomed Investigational Site
Roma, Italy, 00133
Korea, Republic of
Nycomed Investigational Site
Anyang, Korea, Republic of, 431-070
Nycomed Investigational Site
Cheongju, Korea, Republic of, 361-711
Nycomed Investigational Site
Daegu, Korea, Republic of
Nycomed Investigational Site
Seoul, Korea, Republic of, 110-744
Nycomed Investigational Site
Seoul, Korea, Republic of, 120-752
Nycomed Investigational Site
Seoul, Korea, Republic of, 152-703
Nycomed Investigational Site
Wonju, Korea, Republic of, 220-701
Netherlands
Nycomed Investigational Site
's Hertogenbosch, Netherlands, 5200 ME
Nycomed Investigational Site
Amersfoort, Netherlands, 3800 BM
Nycomed Investigational Site
Arnhem, Netherlands, 6815 AD
Nycomed Investigational Site
Enschede, Netherlands, 7500 KA
Nycomed Investigational Site
Heerlen, Netherlands, 6419 PC
Nycomed Investigational Site
Hoorn, Netherlands, 1624 NP
Poland
Nycomed Investigational Site
Bialystok, Poland, 15-540
Nycomed Investigational Site
Bydgoszcz, Poland, 85-681
Nycomed Investigational Site
Gliwice, Poland
Nycomed Investigational Site
Katowice, Poland, 40-753
Nycomed Investigational Site
Lodz, Poland, 90-153
Nycomed Investigational Site
Lodz, Poland, 91-849
Nycomed Investigational Site
Lodz, Poland, 94-010
Nycomed Investigational Site
Lublin, Poland, 20-718
Nycomed Investigational Site
Olesnica, Poland
Nycomed Investigational Site
Ostrow Wielkopolski, Poland, 63-400
Nycomed Investigational Site
Tarnow, Poland, 33-100
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Warszawa, Poland
Nycomed Investigational Site
Wroclaw, Poland, 50-127
Nycomed Investigational Site
Wroclaw, Poland, 53-301
Nycomed Investigational Site
Zawadzkie, Poland, 47-120
Russian Federation
Nycomed Investigational Site
Chelyabinsk, Russian Federation, 454021
Nycomed Investigational Site
Kazan, Russian Federation, 420029
Nycomed Investigational Site
Kemerovo, Russian Federation, 650002
Nycomed Investigational Site
Moscow, Russian Federation, 105077
Nycomed Investigational Site
Moscow, Russian Federation, 117485
Nycomed Investigational Site
Moscow, Russian Federation, 117574
Nycomed Investigational Site
Moscow, Russian Federation, 125206
Nycomed Investigational Site
Nizhniy Novgorod, Russian Federation, 603011
Nycomed Investigational Site
Novosibirsk, Russian Federation, 630087
Nycomed Investigational Site
Novosibirsk, Russian Federation, 630091
Nycomed Investigational Site
Samara, Russian Federation
Nycomed Investigational Site
Saratov, Russian Federation, 410012
Nycomed Investigational Site
Smolensk, Russian Federation, 214006
Nycomed Investigational Site
St Petersburg, Russian Federation, 197706
Nycomed Investigational Site
St. Petersburg, Russian Federation, 196084
Nycomed Investigational Site
St. Petersburg, Russian Federation, 197089
Nycomed Investigational Site
Volgograd, Russian Federation, 400001
Nycomed Investigational Site
Vsevolozhsk, Russian Federation, 188640
Nycomed Investigational Site
Yaroslavl, Russian Federation, 150010
Slovakia
Nycomed Investigational Site
Banska Bystrica, Slovakia, 975 17
Nycomed Investigational Site
Bardejov, Slovakia, 085 01
Nycomed Investigational Site
Bratislava, Slovakia, 821 06
Nycomed Investigational Site
Bratislava, Slovakia, 826 06
Nycomed Investigational Site
Kosice, Slovakia, 040 01
Nycomed Investigational Site
Martin, Slovakia, 036 01
Nycomed Investigational Site
Nitra, Slovakia, 950 01
Nycomed Investigational Site
Nove Zamky, Slovakia, 940 34
Nycomed Investigational Site
Spisska Nova Ves, Slovakia, 052 01
South Africa
Nycomed Investigational Site
Auckland Park, Johannesburg Gauteng, South Africa, 2006
Nycomed Investigational Site
Benoni Gauteng, South Africa, 1500
Nycomed Investigational Site
Bloemfontein Free State, South Africa, 9300
Nycomed Investigational Site
Cape Town Western Cape, South Africa, 7764
Nycomed Investigational Site
Durban Kwazulu-Natal, South Africa, 4092
Nycomed Investigational Site
Johannesburg, South Africa, 2193
Nycomed Investigational Site
Morningside, Johannesburg Gauteng, South Africa, 2057
Nycomed Investigational Site
Thabazimbi Limpopo, South Africa, 0380
Nycomed Investigational Site
Umkomaas Kwazulu-Natal, South Africa, 4170
Nycomed Investigational Site
Witbank Mpumalanga, South Africa, 1035
Spain
Nycomed Investigational Site
Barcelona, Spain, 08022
Nycomed Investigational Site
Guadalajara, Spain, 19002
Nycomed Investigational Site
Madrid, Spain, 28007
Nycomed Investigational Site
Pozuelo de Alarcon, Spain, 28223
Nycomed Investigational Site
Santander, Spain, 39008
Nycomed Investigational Site
Terrassa, Spain, 08221
Nycomed Investigational Site
Valencia, Spain, 46015
Turkey
Nycomed Investigational Site
Ankara, Turkey, 06590
Nycomed Investigational Site
Canakkale, Turkey, 17020
Nycomed Investigational Site
Istanbul, Turkey, 34098
Nycomed Investigational Site
Izmir, Turkey, 35100
Nycomed Investigational Site
Kocaeli, Turkey, 41380
Nycomed Investigational Site
Konya, Turkey, 42075
Nycomed Investigational Site
Mersin, Turkey, 33079
United Kingdom
Nycomed Investigational Site
Edinburgh, United Kingdom, EH16 4TJ
Nycomed Investigational Site
Glasgow, United Kingdom
Nycomed Investigational Site
Liverpool, United Kingdom, L9 7AL
Nycomed Investigational Site
London, United Kingdom, E2 9JX
Nycomed Investigational Site
London, United Kingdom, NW3 2PF
Nycomed Investigational Site
Norwich, United Kingdom, NR4 7UY
Sponsors and Collaborators
Takeda
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01329029     History of Changes
Other Study ID Numbers: RO-2455-404-RD  2010-019685-87  U1111-1141-7422 
Study First Received: March 30, 2011
Results First Received: March 10, 2015
Last Updated: September 25, 2015
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Takeda:
COPD
Roflumilast
Daxas

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

ClinicalTrials.gov processed this record on December 07, 2016