chronic obstructive pulmonary disease (COPD)
Conditions
Interventions
Product Name: Roflumilast 250 µg
Pharmaceutical Form: Tablet
INN or Proposed INN: ROFLUMILAST
CAS Number: 162401-32-3
Concentration unit
Sponsors
TAKEDA DEVELOPMENT CENTRE EUROPE LTD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements. 2. The subject or, when applicable, the subject’s legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. The subject has a history of COPD (according to GOLD 2013[1]) for at least 12 months prior to Screening (Visit V0) associated with chronic productive cough for 3 months in each of the 2 years prior to Screening (Visit V0, with other causes of productive cough excluded). 4. The subject shows a post-bronchodilator FEV1 of =50% of predicted. 5. The subject shows an FEV1/forced vital capacity (FVC) ratio (post-bronchodilator) =65 years) yes F.1.3.1 Number of subjects for this age range 400
Exclusion criteria
Exclusion criteria: 1. The subject has a COPD exacerbation ongoing at the Screening (Visit V0), or has a COPD exacerbation between V0 and V1. 2. The subject has a lower respiratory tract infection not resolved 4 weeks prior to Screening (Visit V0). 3. The subject has a diagnosis of asthma and/or other relevant lung disease (eg, history of primary bronchiectases, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease [eg, fibrosis, silicosis, sarcoidosis], or active tuberculosis). 4. The subject has a known a1-antitrypsin deficiency. 5. The subject has taken roflumilast within 6 months of Screening (Visit V0). Criteria within ethical considerations in terms of general health 6. The subject has clinically relevant abnormal laboratory values suggesting an undiagnosed disease requiring further clinical evaluation (as assessed by the investigator). 7. The subject has a history of severe psychiatric or neurological disorders. 8. The subject has a history of depression associated with suicidal ideation or behavior. 9. The subject has congestive heart failure severity grade IV according to NYHA Functional Classification. 10. The subject has hemodynamically significant cardiac arrhythmias or heart valve deformations. 11. The subject has CT or chest x-ray findings indicating an acute pulmonary disease other than COPD (eg, tuberculosis, severe bronchiectasis, tumors). 12. The subject has severe immunological diseases (eg, known human immune deficiency virus (HIV) infection, multiple sclerosis, lupus erythematosus, progressive multifocal leukoencephalopathy). 13. The subject has liver impairment Child-Pugh B or C and/or active viral hepatitis. 14. The subject has severe acute infectious diseases (eg, tuberculosis, or acute hepatitis). 15. The subject has a history of malignant disease (except basal cell carcinoma) within 5 years before Screening (Visit V0). 16. The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within one year before Screening (Visit V0). 17. The subject has a history of hypersensitivity or allergies to roflumilast or rescue medication or ingredients thereof, or any other contraindication for the use thereof. 18. If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study; or intending to donate ova during such time period. 19. The subject intends to donate blood, organs, or bone marrow during the course of the study. 20. The subject has received any investigational compound within 30 days prior to Screening (Visit V0), is currently participating in another interventional clinical study, or has been previously enrolled in this study. 21. The subject is suspected to be unable or unwilling to comply with study procedures (eg, language problems, psychological disorders, number and timing of visits at the center). 22. The subject suffers from any concomitant disease that might interfere with study procedures or evaluations. 23. The subject is required to take excluded medications (see
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Percentage of subjects prematurely discontinuing study treatment due to any reason (during main period ie, Visit V1 to Vend).;Timepoint(s) of evaluation of this end point: up to week 12; Main Objective: To evaluate discontinuation rates of roflumilast 500µg OD using an up-titration regimen with either 250µg OD or 500µg EOD for the first 4 weeks of treatment followed by 500µg OD for 8 weeks compared with continuous treatment of 500µg OD during the entire 12-week main period. To evaluate if subjects who do not tolerate roflumilast 500µg OD have a drug exposure with 250µg roflumilast OD similar to that observed in other subjects with the 500µg OD dose. ; Secondary Objective: To evaluate the gastro-intestinal tolerability of roflumilast 500µg OD with an up-titration regimen compared with continuous treatment of 500µg OD. To evaluate the safety, discontinuations and tolerability especially the gastro-intestinal tolerability of roflumilast 250µg OD in subjects not tolerating the 500µg OD dose. To evaluate the safety of roflumilast 500µg OD with an up-titration regimen compared with continuous treatment of 500µg OD. To evaluate the efficacy of roflumilast 500µg OD with an up-titration regimen on lung function compared with continuous treatment of 500µg OD. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: as shown in the list above, up to week 12; Secondary end point(s): • Percentage of subjects with adverse events of interest to evaluate tolerability - diarrhea, nausea, headache, decreased appetite, insomnia and abdominal pain (main period, V1 to Vend) • Change in pre-bronchodilator FEV1 during the down-titration period, from V0DT to VendDT • Percentage of subjects prematurely discontinuing study treatment due to any reason (during down-titration period, V0DT to VendDT) Other secondary endpoints for this study are: • Change in pre-bronchodilator FVC and pre-bronchodilator FEV1 from V1 to V2, V3, V4 and Vend (during main period of the study) • To characterize the efficacy of roflumilast 250µg OD on lung function during a down-titration period, in subjects who do not tolerate roflumilast 500µg OD • Change in subject-assessed treatment satisfaction scores from V1 to V2, V3, V4 and Vend (during main period of the study) • To characterize subject-assessed treatment satisfaction of roflumilast 250µg OD during a down-titration period, in subjects who do not tolerate roflumilast 500µg OD. | — |
Countries
Bulgaria, Germany, Greece, Hungary, Korea, Republic of, Philippines, Romania, Russian Federation, Slovakia, South Africa, Thailand, Ukraine, United Kingdom
Contacts
Public ContactCLINICAL STUDY MANAGER
TAKEDA DEVELOPMENT CENTRE EUROPE LTD
Outcome results
None listed