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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)

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Roflumilast

Placebo

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring COPD, Roflumilast, Daxas

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Roflumilast

Placebo

Arm Description

concomitant medication: fixed combination of long-acting β2-agonist and inhaled glucocorticosteroid

Outcomes

Primary Outcome Measures

Rate of Moderate or Severe COPD Exacerbations Per Patient Per Year

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)

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

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

Percentage of Participants Experiencing at Least 1 COPD Exacerbation

Time to First COPD Exacerbation All Categories

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 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

Number of Patients Needed to Treat to Avoid 1 Moderate or Severe COPD Exacerbation Derived From Exacerbation Per Patient Per Year

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

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

Change From Baseline in Post-Bronchodilator Forced Vital Capacity (FVC)

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%)

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)

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

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

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

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

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

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

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

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 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 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 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 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

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

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

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 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 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)

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

Least Square Means was from an ANCOVA model including Last Observation Carried Forward (LOCF).

Change From Baseline in Body Mass Index (BMI)

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.

Full Information

NCT ID

NCT01329029

First Posted

March 30, 2011

Last Updated

October 31, 2016

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT01329029

Brief Title

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

Acronym

REACT

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Completed

Study Start Date

May 2011 (undefined)

Primary Completion Date

March 2014 (Actual)

Study Completion Date

May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Obstructive Pulmonary Disease

Keywords

COPD, Roflumilast, Daxas

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

1945 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Roflumilast

Arm Type

Active Comparator

Arm Description

concomitant medication: fixed combination of long-acting β2-agonist and inhaled glucocorticosteroid

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

concomitant medication: fixed combination of long-acting β2-agonist and inhaled glucocorticosteroid

Intervention Type

Drug

Intervention Name(s)

Roflumilast

Intervention Description

500 µg, once daily

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

once daily

Primary Outcome Measure Information:

Title

Rate of Moderate or Severe COPD Exacerbations Per Patient Per Year

Description

Time Frame

52 weeks

Secondary Outcome Measure Information:

Title

Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in the First Second (FEV1)

Description

Time Frame

Baseline and Week 52

Title

Rate of Severe COPD Exacerbations Per Patient Per Year

Description

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.

Time Frame

52 weeks

Title

Rate of COPD Exacerbations Per Patient Per Year All Categories

Description

Time Frame

52 weeks

Title

Percentage of Participants Experiencing at Least 1 COPD Exacerbation

Description

Time Frame

52 weeks

Title

Time to First COPD Exacerbation All Categories

Description

Time Frame

52 Weeks

Title

Time to Second Moderate or Severe COPD Exacerbation

Description

Time Frame

52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis)

Title

Time to Third Moderate or Severe COPD Exacerbation

Description

Time Frame

52 Weeks

Title

Number of Patients Needed to Treat to Avoid 1 Moderate or Severe COPD Exacerbation Derived From Exacerbation Per Patient Per Year

Description

Time Frame

52 Weeks

Title

Number of Moderate or Severe COPD Exacerbation Days

Description

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.

Time Frame

52 Weeks

Title

Duration of Moderate or Severe COPD Exacerbations Per Participant

Description

Time Frame

52 Weeks

Title

Change From Baseline in Post-Bronchodilator Forced Vital Capacity (FVC)

Description

Time Frame

52 weeks

Title

Change From Baseline in Post-Bronchodilator Forced Expiratory Flow at 25% to 75% of Vital Capacity (FEF25-75%)

Description

Time Frame

52 weeks

Title

Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in the First 6 Seconds (FEV6)

Description

Time Frame

52 weeks

Title

Change From Baseline in Post-Bronchodilator FEV1/FVC

Description

Time Frame

52 weeks

Title

Change From Baseline in Use of Rescue Medication From Daily Diary

Description

Time Frame

Baseline and Week 52

Title

Change From Baseline in COPD Symptom Score From Daily Diary

Description

Time Frame

52 weeks

Title

Percentage of Symptom-Free Days

Description

Symptoms of COPD (cough, sputum) were recorded in a daily diary. The percentage of days without symptoms is reported.

Time Frame

52 Weeks

Title

Percentage of Rescue Medication-Free Days

Description

Participants recorded their use of rescue medication in a daily diary. The percentage of days without rescue medication use.

Time Frame

52 Weeks

Title

Change From Baseline in COPD Assessment Test (CAT) Total Score

Description

Time Frame

Baseline and Week 52

Title

Percentage of Participants With Improvement in CAT

Description

Time Frame

Baseline and Week 52

Title

Time to Mortality Due to Any Reason During the Treatment Period Score

Description

Time to event will be calculated as date of onset of event - date of first intake of double-blind study drug + 1 day.

Time Frame

52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis)

Title

Time to Mortality Due to COPD Exacerbation During the Treatment Period

Description

Time to event will be calculated as date of onset of event - date of first intake of double-blind study drug + 1 day.

Time Frame

52 Weeks

Title

Time to Withdrawal During the Treatment Period

Description

Time to event will be calculated as date of onset of event - date of first intake of double-blind study drug + 1 day.

Time Frame

52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis)

Title

Time to Withdrawal Due to COPD Exacerbation During the Treatment Period

Description

Time to event will be calculated as date of onset of event - date of first intake of double-blind study drug + 1 day.

Time Frame

52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis)

Title

Percentage of Participants With Major Adverse Cardiovascular Event (MACE) During the Treatment Period

Description

Composite MACE is a combined endpoint (cardiovascular death [including death due to undetermined cause], nonfatal myocardial infarction, and nonfatal stroke).

Time Frame

52 Weeks

Title

Time to First Major Adverse Cardiovascular Event (MACE) During the Treatment Period

Description

Time Frame

52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis)

Title

Percentage of Participant With All-Cause Hospitalisation During the Treatment Period

Description

Percentage of patients with at least one hospital admission due to any cause.

Time Frame

52 Weeks

Title

Time to First Hospitalisation Due to Any Cause During the Treatment Period

Description

Time to event will be calculated as date of onset of event - date of first intake of double-blind study drug + 1 day.

Time Frame

52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis)

Title

Time to Trial Withdrawal Due to an Adverse Event

Description

Time to event will be calculated as date of onset of event - date of first intake of double-blind study drug + 1 day.

Time Frame

52 Weeks (some participants extended treatment beyond 52 Weeks and are included in the analysis)

Title

Percentage of Participants Who Experienced at Least 1 Treatment Emergent Adverse Event (TEAE)

Description

Time Frame

52 Weeks

Title

Change From Baseline in Body Weight

Description

Least Square Means was from an ANCOVA model including Last Observation Carried Forward (LOCF).

Time Frame

Baseline and Week 52

Title

Change From Baseline in Body Mass Index (BMI)

Description

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.

Time Frame

Baseline and Week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

AstraZeneca AstraZeneca

Organizational Affiliation

AstraZeneca

Official's Role

Study Director

Facility Information:

Facility Name

Nycomed Investigational Site

City

Box Hill

ZIP/Postal Code

3128

Country

Australia

Facility Name

Nycomed Investigational Site

City

Clayton

ZIP/Postal Code

3168

Country

Australia

Facility Name

Nycomed Investigational Site

City

Concord

ZIP/Postal Code

2139

Country

Australia

Facility Name

Nycomed Investigational site

City

Daws Park

ZIP/Postal Code

5041

Country

Australia

Facility Name

Nycomed Investigational Site

City

Frankston

ZIP/Postal Code

3199

Country

Australia

Facility Name

Nycomed Investigational Site

City

Heidelberg

ZIP/Postal Code

3084

Country

Australia

Facility Name

Nycomed Investigational Site

City

Parkville

ZIP/Postal Code

3050

Country

Australia

Facility Name

Nycomed Investigational Site

City

Toorak Gardens

ZIP/Postal Code

5065

Country

Australia

Facility Name

Nycomed Investigational Site

City

Feldbach

ZIP/Postal Code

8330

Country

Austria

Facility Name

Nycomed Investigational Site

City

Graz

ZIP/Postal Code

8036

Country

Austria

Facility Name

Nycomed Investigational Site

City

Salzburg

ZIP/Postal Code

5020

Country

Austria

Facility Name

Nycomed Investigational Site

City

Wien

ZIP/Postal Code

1140

Country

Austria

Facility Name

Nycomed Investigational Site

City

Bruxelles

ZIP/Postal Code

1000

Country

Belgium

Facility Name

Nycomed Investigational Site

City

Bruxelles

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Nycomed Investigational Site

City

Halen

ZIP/Postal Code

3545

Country

Belgium

Facility Name

Nycomed Investigational Site

City

Liege

ZIP/Postal Code

4000

Country

Belgium

Facility Name

Nycomed Investigational Site

City

Malmedy

ZIP/Postal Code

4960

Country

Belgium

Facility Name

Nycomed Investigational Site

City

Belo Horizonte

Country

Brazil

Facility Name

Nycomed Investigational Site

City

Botucatu

Country

Brazil

Facility Name

Nycomed Investigational Site

City

Florianópolis

Country

Brazil

Facility Name

Nycomed Investigational Site

City

Goiânia

Country

Brazil

Facility Name

Nycomed Investigational Site

City

Porto Alegre

Country

Brazil

Facility Name

Nycomed Investigational Site

City

Rio de Janeiro

Country

Brazil

Facility Name

Nycomed Investigational Site

City

Sao Paolo

Country

Brazil

Facility Name

Nycomed Investigational Site

City

Vitória

Country

Brazil

Facility Name

Nycomed Investigational Site

City

Hamilton

ZIP/Postal Code

L8N 4A6

Country

Canada

Facility Name

Nycomed Investigational Site

City

Kingston

ZIP/Postal Code

K7L 2V7

Country

Canada

Facility Name

Nycomed Investigational Site

City

Lachine

ZIP/Postal Code

H8S 2E4

Country

Canada

Facility Name

Nycomed Investigational Site

City

Niagara Falls

ZIP/Postal Code

L2G 1J4

Country

Canada

Facility Name

Nycomed Investigational Site

City

Richmond Hill

ZIP/Postal Code

L4C 2N9

Country

Canada

Facility Name

Nycomed Investigational Site

City

Toronto

ZIP/Postal Code

M5T 3A9

Country

Canada

Facility Name

Nycomed Investigational Site

City

Toronto

ZIP/Postal Code

M6H 3M2

Country

Canada

Facility Name

Nycomed Investigational Site

City

Winnepeg

ZIP/Postal Code

R2K 3S8

Country

Canada

Facility Name

Nycomed Investigational Site

City

Hellerup

ZIP/Postal Code

2900

Country

Denmark

Facility Name

Nycomed Investigational Site

City

Hillerød

ZIP/Postal Code

3400

Country

Denmark

Facility Name

Nycomed Investigational Site

City

Hvidovre

ZIP/Postal Code

2650

Country

Denmark

Facility Name

Nycomed Investigational Site

City

København NV

ZIP/Postal Code

2400

Country

Denmark

Facility Name

Nycomed Investigational Site

City

Férolles Attilly

ZIP/Postal Code

77150

Country

France

Facility Name

Nycomed Investigational Site

City

Nîmes

ZIP/Postal Code

30900

Country

France

Facility Name

Nycomed Investigational Site

City

Poitiers

ZIP/Postal Code

86021

Country

France

Facility Name

Nycomed Investigational Site

City

Saint-Laurent du Var

ZIP/Postal Code

06700

Country

France

Facility Name

Nycomed Investigational Site

City

Strasbourg

ZIP/Postal Code

67091

Country

France

Facility Name

Nycomed Investigational Site

City

Berlin

ZIP/Postal Code

10367

Country

Germany

Facility Name

Nycomed Investigational Site

City

Berlin

ZIP/Postal Code

10969

Country

Germany

Facility Name

Nycomed Investigational Site

City

Berlin

ZIP/Postal Code

12203

Country

Germany

Facility Name

Nycomed Investigational Site

City

Fürth

ZIP/Postal Code

90766

Country

Germany

Facility Name

Nycomed Investigational Site

City

Großhansdorf

ZIP/Postal Code

22927

Country

Germany

Facility Name

Nycomed Investigational Site

City

Hannover

ZIP/Postal Code

30167

Country

Germany

Facility Name

Nycomed Investigational Site

City

Homburg

ZIP/Postal Code

66421

Country

Germany

Facility Name

Nycomed Investigational Site

City

Koblenz

ZIP/Postal Code

56068

Country

Germany

Facility Name

Nycomed Investigational Site

City

Marburg

ZIP/Postal Code

35043

Country

Germany

Facility Name

Nycomed Investigational Site

City

Rüdersdorf

ZIP/Postal Code

15562

Country

Germany

Facility Name

Nycomed Investigational Site

City

Alexandroupolis

ZIP/Postal Code

68100

Country

Greece

Facility Name

Nycomed Investigational Site

City

Athens

ZIP/Postal Code

10676

Country

Greece

Facility Name

Nycomed Investigational Site

City

Athens

ZIP/Postal Code

11527

Country

Greece

Facility Name

Nycomed Investigational Site

City

Heraklion, Crete

ZIP/Postal Code

71110

Country

Greece

Facility Name

Nycomed Investigational Site

City

Kavala

ZIP/Postal Code

65201

Country

Greece

Facility Name

Nycomed Investigational Site

City

Larissa

ZIP/Postal Code

41100

Country

Greece

Facility Name

Nycomed Investigational Site

City

Marousi

ZIP/Postal Code

15126

Country

Greece

Facility Name

Nycomed Investigational Site

City

Thessaloniki

ZIP/Postal Code

57010

Country

Greece

Facility Name

Nycomed Investigational Site

City

Balassagyarmat

ZIP/Postal Code

2660

Country

Hungary

Facility Name

Nycomed Investigational Site

City

Budapest

ZIP/Postal Code

1125

Country

Hungary

Facility Name

Nycomed Investigational Site

City

Cegléd

ZIP/Postal Code

2700

Country

Hungary

Facility Name

Nycomed Investigational Site

City

Csorna

ZIP/Postal Code

9300

Country

Hungary

Facility Name

Nycomed Investigational Site

City

Deszk

ZIP/Postal Code

6772

Country

Hungary

Facility Name

Nycomed Investigational Site

City

Erd

Country

Hungary

Facility Name

Nycomed Investigational Site

City

Miskolc

ZIP/Postal Code

3526

Country

Hungary

Facility Name

Nycomed Investigational Site

City

Nyíregyháza

ZIP/Postal Code

4400

Country

Hungary

Facility Name

Nycomed Investigational Site

City

Pécs

ZIP/Postal Code

7623

Country

Hungary

Facility Name

Nycomed Investigational Site

City

Siófok

ZIP/Postal Code

8600

Country

Hungary

Facility Name

Nycomed Investigational Site

City

Sopron

ZIP/Postal Code

9400

Country

Hungary

Facility Name

Nycomed Investigational Site

City

Szombathely

ZIP/Postal Code

9700

Country

Hungary

Facility Name

Nycomed Investigational Site

City

Törökbálint

ZIP/Postal Code

2045

Country

Hungary

Facility Name

Nycomed Investigational Site

City

Ashkelon

ZIP/Postal Code

78278

Country

Israel

Facility Name

Nycomed Investigational Site

City

Beer Sheva

ZIP/Postal Code

84101

Country

Israel

Facility Name

Nycomed Investigational Site

City

Haifa

ZIP/Postal Code

31096

Country

Israel

Facility Name

Nycomed Investigational Site

City

Haifa

ZIP/Postal Code

34362

Country

Israel

Facility Name

Nycomed Investigational Site

City

Holon

ZIP/Postal Code

58100

Country

Israel

Facility Name

Nycomed Investigational Site

City

Jerusalem

ZIP/Postal Code

91031

Country

Israel

Facility Name

Nycomed Investigational Site

City

Jerusalm

ZIP/Postal Code

91120

Country

Israel

Facility Name

Nycomed Investigational Site

City

Kfar Saba

ZIP/Postal Code

44281

Country

Israel

Facility Name

Nycomed Investigational Site

City

Petach Tikva

ZIP/Postal Code

49100

Country

Israel

Facility Name

Nycomed Investigational Site

City

Rehovot

ZIP/Postal Code

76100

Country

Israel

Facility Name

Nycomed Investigational Site

City

Tel Aviv

ZIP/Postal Code

67891

Country

Israel

Facility Name

Nycomed Investigational Site

City

Tel Hashomer

ZIP/Postal Code

52621

Country

Israel

Facility Name

Nycomed Investigational Site

City

Tel-Aviv

ZIP/Postal Code

64239

Country

Israel

Facility Name

Nycomed Investigational Site

City

Ferrara

ZIP/Postal Code

44011

Country

Italy

Facility Name

Nycomed Investigational Site

City

Genova

ZIP/Postal Code

16132

Country

Italy

Facility Name

Nycomed Investigational Site

City

Milano

ZIP/Postal Code

20122

Country

Italy

Facility Name

Nycomed Investigational Site

City

Milano

ZIP/Postal Code

20138

Country

Italy

Facility Name

Nycomed Investigational Site

City

Modena

ZIP/Postal Code

41100

Country

Italy

Facility Name

Nycomed Investigational Site

City

Monza

ZIP/Postal Code

20052

Country

Italy

Facility Name

Nycomed Investigational Site

City

Pordenone

ZIP/Postal Code

33170

Country

Italy

Facility Name

Nycomed Investigational Site

City

Roma

ZIP/Postal Code

00133

Country

Italy

Facility Name

Nycomed Investigational Site

City

Anyang

ZIP/Postal Code

431-070

Country

Korea, Republic of

Facility Name

Nycomed Investigational Site

City

Cheongju

ZIP/Postal Code

361-711

Country

Korea, Republic of

Facility Name

Nycomed Investigational Site

City

Daegu

Country

Korea, Republic of

Facility Name

Nycomed Investigational Site

City

Seoul

ZIP/Postal Code

110-744

Country

Korea, Republic of

Facility Name

Nycomed Investigational Site

City

Seoul

ZIP/Postal Code

120-752

Country

Korea, Republic of

Facility Name

Nycomed Investigational Site

City

Seoul

ZIP/Postal Code

152-703

Country

Korea, Republic of

Facility Name

Nycomed Investigational Site

City

Wonju

ZIP/Postal Code

220-701

Country

Korea, Republic of

Facility Name

Nycomed Investigational Site

City

's Hertogenbosch

ZIP/Postal Code

5200 ME

Country

Netherlands

Facility Name

Nycomed Investigational Site

City

Amersfoort

ZIP/Postal Code

3800 BM

Country

Netherlands

Facility Name

Nycomed Investigational Site

City

Arnhem

ZIP/Postal Code

6815 AD

Country

Netherlands

Facility Name

Nycomed Investigational Site

City

Enschede

ZIP/Postal Code

7500 KA

Country

Netherlands

Facility Name

Nycomed Investigational Site

City

Heerlen

ZIP/Postal Code

6419 PC

Country

Netherlands

Facility Name

Nycomed Investigational Site

City

Hoorn

ZIP/Postal Code

1624 NP

Country

Netherlands

Facility Name

Nycomed Investigational Site

City

Bialystok

ZIP/Postal Code

15-540

Country

Poland

Facility Name

Nycomed Investigational Site

City

Bydgoszcz

ZIP/Postal Code

85-681

Country

Poland

Facility Name

Nycomed Investigational Site

City

Gliwice

Country

Poland

Facility Name

Nycomed Investigational Site

City

Katowice

ZIP/Postal Code

40-753

Country

Poland

Facility Name

Nycomed Investigational Site

City

Lodz

ZIP/Postal Code

90-153

Country

Poland

Facility Name

Nycomed Investigational Site

City

Lodz

ZIP/Postal Code

91-849

Country

Poland

Facility Name

Nycomed Investigational Site

City

Lodz

ZIP/Postal Code

94-010

Country

Poland

Facility Name

Nycomed Investigational Site

City

Lublin

ZIP/Postal Code

20-718

Country

Poland

Facility Name

Nycomed Investigational Site

City

Olesnica

Country

Poland

Facility Name

Nycomed Investigational Site

City

Ostrow Wielkopolski

ZIP/Postal Code

63-400

Country

Poland

Facility Name

Nycomed Investigational Site

City

Tarnow

ZIP/Postal Code

33-100

Country

Poland

Facility Name

Nycomed Investigational Site

City

Warszawa

Country

Poland

Facility Name

Nycomed Investigational Site

City

Wroclaw

ZIP/Postal Code

50-127

Country

Poland

Facility Name

Nycomed Investigational Site

City

Wroclaw

ZIP/Postal Code

53-301

Country

Poland

Facility Name

Nycomed Investigational Site

City

Zawadzkie

ZIP/Postal Code

47-120

Country

Poland

Facility Name

Nycomed Investigational Site

City

Chelyabinsk

ZIP/Postal Code

454021

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Kazan

ZIP/Postal Code

420029

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Kemerovo

ZIP/Postal Code

650002

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Moscow

ZIP/Postal Code

105077

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Moscow

ZIP/Postal Code

117485

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Moscow

ZIP/Postal Code

117574

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Moscow

ZIP/Postal Code

125206

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Nizhniy Novgorod

ZIP/Postal Code

603011

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Novosibirsk

ZIP/Postal Code

630087

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Novosibirsk

ZIP/Postal Code

630091

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Samara

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Saratov

ZIP/Postal Code

410012

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Smolensk

ZIP/Postal Code

214006

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

St Petersburg

ZIP/Postal Code

197706

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

St. Petersburg

ZIP/Postal Code

196084

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

St. Petersburg

ZIP/Postal Code

197089

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Volgograd

ZIP/Postal Code

400001

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Vsevolozhsk

ZIP/Postal Code

188640

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Yaroslavl

ZIP/Postal Code

150010

Country

Russian Federation

Facility Name

Nycomed Investigational Site

City

Banska Bystrica

ZIP/Postal Code

975 17

Country

Slovakia

Facility Name

Nycomed Investigational Site

City

Bardejov

ZIP/Postal Code

085 01

Country

Slovakia

Facility Name

Nycomed Investigational Site

City

Bratislava

ZIP/Postal Code

821 06

Country

Slovakia

Facility Name

Nycomed Investigational Site

City

Bratislava

ZIP/Postal Code

826 06

Country

Slovakia

Facility Name

Nycomed Investigational Site

City

Kosice

ZIP/Postal Code

040 01

Country

Slovakia

Facility Name

Nycomed Investigational Site

City

Martin

ZIP/Postal Code

036 01

Country

Slovakia

Facility Name

Nycomed Investigational Site

City

Nitra

ZIP/Postal Code

950 01

Country

Slovakia

Facility Name

Nycomed Investigational Site

City

Nove Zamky

ZIP/Postal Code

940 34

Country

Slovakia

Facility Name

Nycomed Investigational Site

City

Spisska Nova Ves

ZIP/Postal Code

052 01

Country

Slovakia

Facility Name

Nycomed Investigational Site

City

Auckland Park, Johannesburg Gauteng

ZIP/Postal Code

2006

Country

South Africa

Facility Name

Nycomed Investigational Site

City

Benoni Gauteng

ZIP/Postal Code

1500

Country

South Africa

Facility Name

Nycomed Investigational Site

City

Bloemfontein Free State

ZIP/Postal Code

9300

Country

South Africa

Facility Name

Nycomed Investigational Site

City

Cape Town Western Cape

ZIP/Postal Code

7764

Country

South Africa

Facility Name

Nycomed Investigational Site

City

Durban Kwazulu-Natal

ZIP/Postal Code

4092

Country

South Africa

Facility Name

Nycomed Investigational Site

City

Johannesburg

ZIP/Postal Code

2193

Country

South Africa

Facility Name

Nycomed Investigational Site

City

Morningside, Johannesburg Gauteng

ZIP/Postal Code

2057

Country

South Africa

Facility Name

Nycomed Investigational Site

City

Thabazimbi Limpopo

ZIP/Postal Code

0380

Country

South Africa

Facility Name

Nycomed Investigational Site

City

Umkomaas Kwazulu-Natal

ZIP/Postal Code

4170

Country

South Africa

Facility Name

Nycomed Investigational Site

City

Witbank Mpumalanga

ZIP/Postal Code

1035

Country

South Africa

Facility Name

Nycomed Investigational Site

City

Barcelona

ZIP/Postal Code

08022

Country

Spain

Facility Name

Nycomed Investigational Site

City

Guadalajara

ZIP/Postal Code

19002

Country

Spain

Facility Name

Nycomed Investigational Site

City

Madrid

ZIP/Postal Code

28007

Country

Spain

Facility Name

Nycomed Investigational Site

City

Pozuelo de Alarcon

ZIP/Postal Code

28223

Country

Spain

Facility Name

Nycomed Investigational Site

City

Santander

ZIP/Postal Code

39008

Country

Spain

Facility Name

Nycomed Investigational Site

City

Terrassa

ZIP/Postal Code

08221

Country

Spain

Facility Name

Nycomed Investigational Site

City

Valencia

ZIP/Postal Code

46015

Country

Spain

Facility Name

Nycomed Investigational Site

City

Ankara

ZIP/Postal Code

06590

Country

Turkey

Facility Name

Nycomed Investigational Site

City

Canakkale

ZIP/Postal Code

17020

Country

Turkey

Facility Name

Nycomed Investigational Site

City

Istanbul

ZIP/Postal Code

34098

Country

Turkey

Facility Name

Nycomed Investigational Site

City

Izmir

ZIP/Postal Code

35100

Country

Turkey

Facility Name

Nycomed Investigational Site

City

Kocaeli

ZIP/Postal Code

41380

Country

Turkey

Facility Name

Nycomed Investigational Site

City

Konya

ZIP/Postal Code

42075

Country

Turkey

Facility Name

Nycomed Investigational Site

City

Mersin

ZIP/Postal Code

33079

Country

Turkey

Facility Name

Nycomed Investigational Site

City

Edinburgh

ZIP/Postal Code

EH16 4TJ

Country

United Kingdom

Facility Name

Nycomed Investigational Site

City

Glasgow

Country

United Kingdom

Facility Name

Nycomed Investigational Site

City

Liverpool

ZIP/Postal Code

L9 7AL

Country

United Kingdom

Facility Name

Nycomed Investigational Site

City

London

ZIP/Postal Code

E2 9JX

Country

United Kingdom

Facility Name

Nycomed Investigational Site

City

London

ZIP/Postal Code

NW3 2PF

Country

United Kingdom

Facility Name

Nycomed Investigational Site

City

Norwich

ZIP/Postal Code

NR4 7UY

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

29797235

Citation

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.

Results Reference

derived

PubMed Identifier

29763572

Citation

Martinez FJ, Rabe KF, Calverley PMA, Fabbri LM, Sethi S, Pizzichini E, McIvor A, Anzueto A, Alagappan VKT, Siddiqui S, Reisner C, Zetterstrand S, Roman J, Purkayastha D, Bagul N, Rennard SI. Determinants of Response to Roflumilast in Severe Chronic Obstructive Pulmonary Disease. Pooled Analysis of Two Randomized Trials. Am J Respir Crit Care Med. 2018 Nov 15;198(10):1268-1278. doi: 10.1164/rccm.201712-2493OC.

Results Reference

derived

PubMed Identifier

28679611

Citation

Rabe KF, Calverley PMA, Martinez FJ, Fabbri LM. Effect of roflumilast in patients with severe COPD and a history of hospitalisation. Eur Respir J. 2017 Jul 5;50(1):1700158. doi: 10.1183/13993003.00158-2017. Print 2017 Jul. No abstract available.

Results Reference

derived

PubMed Identifier

25684586

Citation

Martinez FJ, Calverley PM, Goehring UM, Brose M, Fabbri LM, Rabe KF. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial. Lancet. 2015 Mar 7;385(9971):857-66. doi: 10.1016/S0140-6736(14)62410-7. Epub 2015 Feb 13.

Results Reference

derived

PubMed Identifier

22791991

Citation

Calverley PM, Martinez FJ, Fabbri LM, Goehring UM, Rabe KF. Does roflumilast decrease exacerbations in severe COPD patients not controlled by inhaled combination therapy? The REACT study protocol. Int J Chron Obstruct Pulmon Dis. 2012;7:375-82. doi: 10.2147/COPD.S31100. Epub 2012 Jun 20.

Results Reference

derived

Learn more about this trial

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

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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)

Chronic Obstructive Pulmonary Disease

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial