Pharmacokinetic Interaction Study Between Budesonide and Metronidazole in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to describe a possible effect of metronidazole on PK of budesonide in healthy volunteers.

Detailed Description
-----------------
The primary objective of this study is to describe a possible effect of metronidazole on PK of budesonide in healthy volunteers. Secondary objectives: Effect of budesonide on metronidazole steady-state PK (primarily described as area under the concentration-time-curve). Urinary 6β-hydroxycortisol (being a marker of CYP3A activity) and cortisol excretion before and during metronidazole multiple-dose co-administration. Safety parameters.

Official Title
-----------------
Pharmacokinetic Interaction Study Between Budesonide and Metronidazole in Healthy Volunteers

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Budesonide 2 single doses, Metronidazole multiple-dose


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|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.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| other PK parameters |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
healthy volunteers