Official Title: “Pharmacokinetic Interaction Study Between Budesonide and Metronidazole in Healthy Volunteers”

The primary objective of this study is to describe a possible effect of metronidazole on PK of budesonide in healthy volunteers.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics/Dynamics Study

The primary objective of this study is to describe a possible effect of metronidazole on PK of budesonide in healthy volunteers.

Secondary objectives:

1. Effect of budesonide on metronidazole steady-state PK (primarily described as area under the concentration-time-curve).

2. Urinary 6β-hydroxycortisol (being a marker of CYP3A activity) and cortisol excretion before and during metronidazole multiple-dose co-administration.

3. Safety parameters.

Intervention(s) in this Clinical Trial

• Drug: Budesonide 2 single doses, Metronidazole multiple-dose
  • Budesonide 3 mg single oral dose on Day 1 and Day 9. Metronidazole 750 mg b.i.d. from Day 2 until Day 8, Metronidazole 750 mg once daily (in the morning) on Day 9.

Primary Measures

• AUC

Secondary Measures

• other PK parameters

Inclusion Criteria:

• Healthy male subjects
• Caucasian origin
• Age: between 18 and 55 years (inclusive)
• Body mass index (BMI) within 18-30 kg/m²
• Body weight at least 50 kg, at most 100 kg
• Non-smoker (or ex-smoker ≥1 year), proven by urine cotinine <500 ng/ml
• Clinically acceptable supine blood pressure and pulse rate, i.e. BP 100-145 mmHg systolic, 60-90 mmHg diastolic and pulse rate 50-100 bpm
• Normal ECG
• Participants must perform an adequate contraception during the study and until 6 months after the last dose of the present trial
• Ability to communicate well with the investigator and comply with the requirements of the entire study
• Written consent

Exclusion Criteria:

• Subjects with contraindications for budesonide
• Subjects with contraindications for metronidazole
• History or current clinical evidence of any cardiac, cardio-vascular, pulmonary, gastrointestinal, (cholangio-)hepatic, renal, endocrine, neurological, musculoskeletal, ophthalmological, infectious, haematological, oncological, psychiatric, or other acute or chronic diseases and/or pathological findings which might interfere with the drugs' safety, tolerability, absorption and/or pharmacokinetics
• History or current evidence of clinically relevant allergies or idiosyncrasy to drugs or food
• Clinically relevant abnormalities in clinical chemical, hematological or any other laboratory variables
• Current smoker or ex-smoker ≤ 1 year
• Excessive alcohol consumption (³ 35 g/day in males)
• Abuse of drugs
• Positive drug screening
• Positive anti-HIV-test, HBsAg-test or anti-HCV-test
• Proneness to orthostatic dysregulation, faintings, or blackouts
• Heavy tea or coffee drinkers (more than 1 l ≈ 6 cups per day)
• Administration of glucocorticosteroids within 6 weeks prior to study day 1 or during the trial
• Repeated use of drugs during the last 4 weeks prior to study day 1 or during the trial, which might influence hepatic biotransformation
• Any medication including OTC medication within the last 14 days prior to study day 1 or during the trial (single intake of a drug may be accepted if judged by the investigators to have no clinical relevance and no relevance for the study objectives)
• Intake of grapefruit-containing food or beverages within 7 days prior to study day 1 or during the trial
• Clinically relevant acute or chronic bacterial, fungal or viral infections
• Surgery of the gastrointestinal tract which may interfere with drug absorption (not applicable for minor abdominal surgery such as e.g. appendectomy and herniotomy)
• Vegetarian diet or other peculiar dietary habits which would preclude the subject's acceptance of standardized (non-vegetarian) meals
• Subjects suspected or known not to follow instructions
• Subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study
• Patients known to be in financial difficulties, which could interfere with their appraisal of the informative instructions
• Vulnerable subjects (e.g., persons kept in detention or persons who are depending on the sponsor or the investigator)
• Blood donation or other blood loss of more than 400 ml within the last 2 months prior to study day 1
• Participation in a clinical trial within the last 2 months prior to study day 1 (assessed by anamnestic inquiry)

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: University Hospital Tuebingen

Overall Clinical Trial Officials and Contacts

Christoph H Gleiter, MD Principal Investigator Department of Clinical Pharmacology  

Information obtained from ClinicalTrials.gov on August 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00338910

Study ID Number: BUC-58/BIO

ClinicalTrials.gov Identifier: NCT00338910

Health Authority: Germany: Federal Institute for Drugs and Medical Devices