NCT02165826

Evaluation of Tolerability and Pharmacokinetics of Roflumilast, 250μg and 500μg, as add-on to Standard COPD Treatment to Treat Severe COPD

A Multicenter, Randomized, Double-blind Phase 3 Study to Evaluate Tolerability and Pharmacokinetics of 500 μg Roflumilast Once Daily With an Up-titration Regimen in COPD, Including an Open-label Down-titration Period Evaluating Tolerability and Pharmacokinetics of 250 μg Roflumilast Once Daily in Subjects Not Tolerating 500 μg Roflumilast Once-daily

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,323 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 40 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Chronic Obstructive Pulmonary Disease (COPD)

Interventions

Type	Name	Description
DRUG	Roflumilast	Roflumilast tablets
DRUG	Roflumilast Placebo	Roflumilast placebo-matching tablets
DRUG	Standard of Care COPD Treatment	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.

Timeline

• Start date: 2014-05-01
• Primary completion: 2015-09-01
• Completion: 2015-09-01
• First posted: 2014-06-18
• Last updated: 2017-04-20
• Results posted: 2017-03-14

Locations

2 sites across 1 country: Slovakia