Pharmacodynamic/Pharmacokinetic Interactions Between Oral Roflumilast and Inhaled Formoterol

AstraZeneca

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: Roflumilast

Study type

Interventional

Funder types

Industry

Identifiers

NCT00940329

BY217/CP-059

Details and patient eligibility

About

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.

Enrollment

27 patients

Sex

Male

Ages

18 to 45 years old

Volunteers

Accepts Healthy Volunteers

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)