Pharmacodynamic/Pharmacokinetic Interactions Between Oral Roflumilast and Inhaled Formoterol

Study Overview
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Brief Summary
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This Phase I, open, randomized controlled, multiple-dose, parallel-group study investigated the potential pharmacodynamic and pharmacokinetic interactions between multiple doses of oral roflumilast and inhaled formoterol. Healthy male subjects were assigned to treatment A or treatment B. Subjects in treatment A received 500 μg/d roflumilast from day 2 to day 18 and 48 μg/d formoterol from day 12 to day 18. Subjects in treatment B received 48 μg/d formoterol from day 2 to day 18 and 500 μg/d roflumilast from day 9 to day 18. Impedance cardiography, ECG, serum potassium and glucose concentrations and effects on blood eosinophils assessed potential pharmacodynamic interactions. In addition, the safety and tolerability were evaluated. Pharmacokinetic parameters were assessed for roflumilast, roflumilast N-oxide, and formoterol.

Official Title
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Investigation on the Cardiovascular and Pharmacokinetic Interaction Between Oral Roflumilast and Inhaled Formoterol in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Roflumilast
* Drug: Roflumilast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 45 years Normal body weight as indicated by a Body Mass Index (BMI) between 18 and 30 kg/m2 and a body weight > 50 kg Assessed as healthy, based on a screening examination including medical history, physical examination, BP, PuR, ECG, and clinical laboratory results Caucasian Exclusion Criteria: Suspected lack of compliance Participant in any other study or donation of blood during the last 30 d before start of this study (last day of intake of medication - first day of medication in the following study) Any active disease, acute or chronic (also psychiatric diseases) Any signs or present history of cardiac diseases (e.g. QTc interval acc. to Bazett ≥ 430 ms, PQ ≥ 220 ms), in particular tachycardiac arrhythmia, third-degree AV-block, idiopathic-subvalvular aortic stenosis or hypertrophic-obstructive cardiomyopathia Proneness to symptomatic orthostatic dysregulation, fainting or blackouts (medical history), or to orthostatic hypotension defined by SBP < 90 mm Hg (standing blood pressure, 30 s after raising up from a supine position) Gastrointestinal surgery except from appendectomy and herniotomy HIV or hepatitis screening positive or not performed (in case of a positive HIV test, the subject had to be informed by a physician in personal communication Drug screening positive or not performed Excessive xanthine consumption (more than 5 cups of coffee or equivalent per day) Non-compliance for measurements of impedance cardiography (feasibility was proven and documented at the screening visit by one test procedure)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment A<br> | Drug: Roflumilast<br>* Treatment A (500 μg/d roflumilast from day 2 to day 18 and 48 μg/d formoterol from day 12 to day 18)<br>|
| Active Comparator: Treatment B<br> | Drug: Roflumilast<br>* Treatment B (48 μg/d formoterol from day 2 to day 18 and 500 μg/d roflumilast from day 9 to day 18)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Potential cardiovascular interaction (exploratory) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Potential pharmacokinetic interactions and potential pharmacodynamic interactions |  |  | 
| Safety and tolerability of the monotreatments and the combination treatment (exploratory) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug interactions, Pharmacodynamic interactions, Pharmacokinetic interactions, Formoterol, Healthy subjects, Phase I study, Roflumilast