Clinical trial NCT00940329: Pharmacodynamic/Pharmacokinetic Interactions Between Oral Roflumilast and Inhaled Formoterol
Official title: Investigation on the Cardiovascular and Pharmacokinetic Interaction Between Oral Roflumilast and Inhaled Formoterol in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Drug interactions
Pharmacodynamic interactions
Pharmacokinetic interactions
Formoterol
Healthy subjects
Phase I study
Roflumilast
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2009-07-16
Enrollment: 27
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Potential cardiovascular interaction (exploratory)
Secondary outcomes:
measure: Potential pharmacokinetic interactions and potential pharmacodynamic interactions
measure: Safety and tolerability of the monotreatments and the combination treatment (exploratory)
Other outcomes:
Locations:
city: Konstanz
country: Germany
facility: Nycomed
Study officials:
affiliation: AstraZeneca
name: AstraZeneca AstraZeneca
role: STUDY_DIRECTOR
References:
citation: de Mey C, Nassr N, Lahu G. No relevant cardiac, pharmacokinetic or safety interactions between roflumilast and inhaled formoterol in healthy subjects: an open-label, randomised, actively controlled study. BMC Clin Pharmacol. 2011 Jun 1;11:7. doi: 10.1186/1472-6904-11-7.