Pharmacodynamic/Pharmacokinetic Interactions Between Oral Roflumilast and Inhaled Formoterol

This study has been completed.
Information provided by:
Nycomed Identifier:
First received: July 3, 2009
Last updated: May 4, 2012
Last verified: May 2012
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.

Condition Intervention Phase
Drug: Roflumilast
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Investigation on the Cardiovascular and Pharmacokinetic Interaction Between Oral Roflumilast and Inhaled Formoterol in Healthy Subjects

Resource links provided by NLM:

Further study details as provided by Nycomed:

Primary Outcome Measures:
  • Potential cardiovascular interaction (exploratory)

Secondary Outcome Measures:
  • Potential pharmacokinetic interactions and potential pharmacodynamic interactions
  • Safety and tolerability of the monotreatments and the combination treatment (exploratory)

Enrollment: 27
Study Start Date: April 2004
Study Completion Date: December 2004
Primary Completion Date: July 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Treatment A Drug: Roflumilast
Treatment A (500 μg/d roflumilast from day 2 to day 18 and 48 μg/d formoterol from day 12 to day 18)
Active Comparator: Treatment B Drug: Roflumilast
Treatment B (48 μg/d formoterol from day 2 to day 18 and 500 μg/d roflumilast from day 9 to day 18)


Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

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)
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Please refer to this study by its identifier: NCT00940329

Konstanz, Germany, 78467
Sponsors and Collaborators
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Head of Exploratory Clinical Development, Nycomed GmbH Identifier: NCT00940329     History of Changes
Other Study ID Numbers: BY217/CP-059 
Study First Received: July 3, 2009
Last Updated: May 4, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Nycomed:
Drug interactions
Pharmacodynamic interactions
Pharmacokinetic interactions
Healthy subjects
Phase I study

Additional relevant MeSH terms:
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses processed this record on May 05, 2016