A 52-week, Double-Blind, Randomized, Placebo Controlled Parallel Group Study to Evaluate the Effect of Roflumilast 500 ?g on Exacerbation Rate in Subjects with Chronic Obstructive Pulmonary Disease (COPD) Treated with a Fixed Dose Combination of Long-Acting Beta Agonist and Inhaled Corticosteroid (LABA/ICS)

Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2011-003606-24-ES

Lead Sponsor: Forest Research Institute, Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 2300

Inclusion Criteria

Inclusion Criteria at Screening (Visit 1)

1. Male or female subjects at least 40 years of age

2. History of COPD (according to GOLD 2010) for at least 12 months prior to Screening (Visit 1) associated with chronic productive cough for 3 months in each of 2 consecutive years (with other causes of productive cough excluded). Only subjects with chronic bronchitis will be included.

3. Forced expiratory volume after 1 second (FEV1)/forced vital capacity (FVC) ratio (postbronchodilator) < 70% at Screening (Visit 1)

4. FEV1 (postbronchodilator)
5. At least two documented moderate or severe COPD exacerbations within 12 months prior to Screening (Visit 1)

6. Subjects must be on FDC LABA/ICS (Advair® 250/50?g 1 puff BID or, Symbicort® 160/4.5 ?g 2 puffs BID) concomitant treatment >or= 3 months prior to Screening (Visit 1)

7. Those subjects who were previously treated with LAMA must have been on a stable dose for >or= 3 months before Screening (Visit 1) and must continue on the same dose throughout the study

8. Former smoker (defined as smoking cessation at least 1 year ago) or current smoker both with a smoking history of at least 20 pack-years

9. Subjects must be able to perform repeatable pulmonary function testing for FEV1 according to ATS/ERS 2005 criteria

10. Women of childbearing potential with a negative urine pregnancy test at Screening with ongoing use of birth control from study start (Screening) to last subject visit (Visit 8)

11. Subjects judged by the Investigator to be physically capable of participating in a year-long study based on medical history, physical examination, ECG, and routine laboratory data evaluations

12. Subjects who understand the study procedures and are willing to participate in the study as indicated by signing the informed consent

Inclusion Criteria at Randomization (Visit 2)

13. No moderate or severe COPD exacerbations between Screening (Visit 1) and Randomization (Visit 2)

14. Tablet compliance >or= 80% and
15. Advair and Symbicort compliance of >or= 80% and
16. Subjects must have remained on the same COPD maintenance therapy between Screening (Visit 1) and Randomization (Visit 2) (ie, ICS/LABA or LAMA added onto FDC LABA/ICS)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2070
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 230

Exclusion Criteria

1. Severe or very severe COPD exacerbation and/or COPD exacerbations treated with antibiotics or systemic glucocorticosteroids within 4 weeks of Screening (Visit 1) (ie, subjects must be clinically stable)

2. Lower respiratory tract infection within 4 weeks of Screening (Visit 1)

3. Diagnosis of significant lung disease other than COPD (eg, history of primary bronchiecstasis, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease [eg, fibrosis, silicosis, sarcoidosis], or active tuberculosis, pulmonary thromboembolic disease), pulmonary resection or lung volume surgery during the
past 12 months, cystic fibrosis, Kartagener syndrome), post organ transplantation, or who are expected to require thoracotomy or other lung surgery during the study

4. Known alpha-1-antitrypsin deficiency

5. Current diagnosis of asthma (either controlled or uncontrolled)

6. Liver impairment Child-Pugh B or C and/or active viral hepatitis

7. Chronic use of oxygen therapy >or= 15 hours/day

8. Body mass index (BMI) >or= 45 kg/m2

9. Subjects who have participated in an acute pulmonary rehabilitation program within the previous 3 months. (Note: Subjects on a stable pulmonary rehabilitation exercise regimen for at least 6 weeks are not excluded)

10. Subjects with a history of suicidal behavior
11. Subjects with a screening Columbia Suicide Severity Rating Scale (C-SSRS) score of >or= 4 (suicidal ideation or behavior)

12. Subjects with clinically significant cardiovascular conditions including: myocardial infarction within the previous 6 months; newly diagnosed arrhythmia within the previous 3 months; unstable angina; unstable arrhythmia that has required changes in pharmacological therapy or other intervention (eg, use of an automated implantable cardioverter-defibrillator); hospitalization within the previous 12 months for heart failure functional classes III (marked limitation of activity and only comfortable at rest) and IV (need of complete rest, confinement to bed or chair, discomfort at
any physical activity, and presence of symptoms at rest) (New York Heart Association criteria [NYHA])

13. Subjects with a QTc (calculated according to Bazett?s formulae [QTc = QT/RR2], as indicated in the paper tracing generated by the equipment used to record the ECGs) above 470 milliseconds in the resting ECGs performed at Screening (Visit 1)

14. Subjects with clinically relevant abnormalities (as judged by the PI or Study Physician) in the results of the clinical laboratory tests, in ECG parameters other than QTc, or in the physical examination or vital signs at Screening (Visit 1) except for those related to COPD

15. Subjects who are HIV positive or have active viral hepatitis or other chronic systemic infection

16. Subjects with a history of drug or alcohol abuse within the previous 5 years

17. Subjects with any other serious or uncontrolled physical or mental condition/disease that, as judged by the Investigator, could place the subject at higher risk derived from his/her participation in the study, could confound the results of the study, or would be
likely to prevent the subject from complying with the requirements of the study or completing the study. If there is a history of such disease but the condition has been stable for more than 1 year and is judged by the PI not to interfere with the subject?s participation in the study, the subject may b