Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: Drug therapy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1323
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate discontinuation rates of roflumilast using an up-titration regimen for the first 4 weeks of treatment compared with continuous treatment of 500 μg one daily (OD) during the entire 12-week main period, and to evaluate if participants who do not tolerate roflumilast 500 μg OD have a drug exposure with 250 μg roflumilast OD similar to that observed in other participants with the 500 μg OD dose.

Detailed description:
Roflumilast is a product which has been approved for the treatment of severe chronic obstructive lung disease (COPD) and its approved dose is 500μg once daily. This study is primarily designed to see whether alternation in this dose can improve tolerability of Roflumilast in COPD patients. Therefore one in three patients will start roflumilast therapy at a lower dose of 250μg once daily, another one in three will only take the 500μg tablet every other day (and one placebo every other day). Rest of them will start the regular dose of 500μg once daily right away and see whether starting with a lower dose of Roflumilast will lead to better tolerability. Furthermore, the study will see if patients who do not tolerate roflumilast should be given a lower dose of 250μg once daily.

Lastly, the study will investigate what the body does to roflumilast. Patients with a history of COPD for at least last 12 months and a former smoker or current smoker with history of at least 10 pack years will be invited to participate.

The main study period lasts for a maximum of 15 weeks and patients will have to visit the study site up to 6 times. If patients are not tolerating roflumilast, the investigators may switch them to the down titration period where they may be on a lower dose for rest of the study. Then patients will remain in the down titration period for additional 8 weeks and will have to visit the study site 4 times. Most of the visits will take approximately 1 to 2 hours. However, one visit in the main period and 1 or 2 visits in the down titration period will take approximately 6 to 7 hours. These visits are longer to allow time to conduct blood taking.

The Randomization visit is considered the Baseline visit and for participants that discontinue the Main Period and continue into the Down-Titration Period Day 1 of Down Titration is considered BaselineDT.

Arms:
arm 1: Roflumilast 500 μg tablets, orally, once daily for 12 weeks. Any participants not tolerating study treatment will be prematurely discontinued and will receive roflumilast 250 μg, tablets, orally, once daily for 8 weeks. arm 2: Roflumilast 500 μg, tablets, orally, every other day, and roflumilast placebo-matching tablets, orally, every other day on non-treatment days, for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks. Any participants not tolerating study treatment will be prematurely discontinued and will receive roflumilast 250 μg, tablets, orally, once daily for 8 weeks. arm 3: Roflumilast 250 μg, tablets, orally, once daily for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks. Any participants not tolerating study treatment will be prematurely discontinued and will receive roflumilast 250 μg, tablets, orally, once daily for 8 weeks.

Interventions: intervention 1: Roflumilast intervention 2: Roflumilast Placebo intervention 3: Standard of Care COPD Treatment
Intervention descriptions: intervention 1: Roflumilast tablets intervention 2: Roflumilast placebo-matching tablets intervention 3: The participant is on standard of care COPD maintenance treatment including LABAs, long-acting anticholinergics, or any combination thereof taken on a constant daily dose within 12 weeks prior to Screening (Visit V0) Examples of LABA containing products are: Formoterol, Salmeterol, Indacaterol, Formoterol/Budesonide, Salmeterol/Fluticasone, Treatment including lon-acting anticholinergics: Tiotropium, Aclidinium.

Protocol document: