Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Interventions
Trade Name: Daliresp®
Product Name: Roflumilast Tablet, 500 microg
Pharmaceutical Form: Tablet
INN or Proposed INN: ROFLUMILAST
CAS Number: 162401-32-3
Current Sponsor code: BYK20869, B9302-107, BY217
Sponsors
Forest Research Institute, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
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) 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 or= 80% and =65 years) yes F.1.3.1 Number of subjects for this age range 230
Exclusion criteria
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the additional benefit of roflumilast added on to fixed dose combination LABA/ICS (Advair® 250/50?g 1 puff b.i.d or, Symbicort® 160/4.5?g 2 puffs b.i.d) in the reduction of exacerbations in subjects with severe to very severe COPD.;Secondary Objective: The key secondary objectives will evaluate the effects of roflumilast on lung function (spirometry), COPD symptoms (as collected in diaries), and the safety and tolerability of roflumilast in COPD subjects concomitantly treated with FDC LABA/ICS.;Primary end point(s): The primary efficacy endpoint of the study is the rate of moderate or severe COPD exacerbations per subject per year. Mild exacerbations are defined by increased use of rescue medication 3 or more puffs/day on at least 2 consecutive days during the double-blind treatment period. Moderate exacerbations are defined as a worsening of COPD symptoms necessitating oral or parenteral glucocorticosteroids. Severe exacerbations are defined as worsening of COPD resulting in hospitalization and/or leading to death;Timepoint(s) of evaluation of this end point: Week 4, 12, 20, 28, 40 and 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoint is the change from randomization (Visit 2) over 52 weeks of treatment in prebronchodilator FEV1. Additional Efficacy Endpoints * COPD exacerbation parameters - Rate of exacerbations in the following categories: mild, moderate, severe, treated with systemic steroids and/or antibiotics, treated with antibiotic therapy only, moderate or severe and/or treated with antibiotics, exacerbations that lead to COPD-related emergency room visit or hospitalization or death, exacerbations derived from the Exacerbations Chronic Pulmonary Disease Tool - Patient Reported Outcome (EXACT-PRO) questionnaire, and exacerbations as reported on the eCRF - Proportion of subject with at least one exacerbation for all categories including moderate or severe exacerbation - Time to first, second, and third moderate or severe exacerbations - Number needed to treat (NNT) to avoid one moderate or severe COPD exacerbation per subject per year - Number of COPD exacerbation days (all categories) - Duration of COPD exacerbations (all categories) - The algorithm for deriving COPD exacerbations from EXACT-PRO questionnaire will be described in the Statistical Analysis Plan (SAP) * Spirometry parameters, mean change from baseline over post-randomization visits during treatment period in - FVC: Forced vital capacity (expiratory) - FEV1/FVC: Ratio of forced expiratory volume after 1 second to forced vital capacity - FEV6: Forced expiratory volume in the first 6 seconds * Diary parameters, mean change from baseline over post-randomization visits during treatment period in - Rescue medication use (puffs/day) - EXACT total score, and scores from the Breathlessness, Cough & Sputum, and Chest domains (daily score derived from EXACT-PRO questionnaire);Timepoint(s) of evaluation of this end point: Week 4, 12, 20, 28, 40 and 52 | — |
Countries
Argentina, Canada, Chile, Colombia, Germany, Italy, Latvia, Malaysia, Mexico, Peru, Philippines, Romania, Russian Federation, Serbia, Spain, Taiwan, Thailand, Ukraine, United States
Contacts
Public ContactForest Medical Information and Comm
Forest Laboratories Inc.
Outcome results
None listed