Pharmacodynamic/Pharmacokinetic Interactions Between Oral Roflumilast and Inhaled Formoterol

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Roflumilast

• Registration Number: NCT00940329
• Lead Sponsor: AstraZeneca

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2004-04
• Primary Completion: 2004-07
• Study Completion: 2004-12
• Study First Submitted: 2009-07-03
• Study First Submitted QC: 2009-07-15
• Study First Posted: 2009-07-16
• Status Verified: 2016-09
• Last Update Submitted: 2016-12-01
• Last Update Posted: 2016-12-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 27

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment A	Roflumilast	-
Treatment B	Roflumilast	-

Primary Outcome Measures

Name	Time	Method
Potential cardiovascular interaction (exploratory)

Secondary Outcome Measures

Name	Time	Method
Potential pharmacokinetic interactions and potential pharmacodynamic interactions
Safety and tolerability of the monotreatments and the combination treatment (exploratory)

Trial Locations

Locations (1)

Nycomed; 🇩🇪 Konstanz, Germany