Assessment of Target Site Pharmacokinetics of Voriconazole in Healthy Volunteers During Sequence Therapy

• Status: Completed
• Trial end date: 2013-08-01
• Target enrollment: 0
• Participant gender: Male

Summary

The present study aims at measuring unbound voriconazole concentrations in plasma and at the relevant target site of systemic fungal infections, i.e. the interstitial space fluid of soft tissues, to assess the target site pharmacokinetics. For this purpose the microdialysis technique will be employed which is capable of measuring the unbound, microbiologically active concentration of antifungals in the interstitial space fluid of virtually all tissues. This is the first human study of this drug employing the microdialysis technique determining the target site concentrations over several days (single and multiple dosing).

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Martin-Luther-Universität Halle-Wittenberg
• Collaborator: Medical University of Vienna
• Treatments: Voriconazole

Criteria

Inclusion Criteria:

• Healthy males aged between 18 and 50 years

• Body mass index between 20 and 28

• Known genotype of CYP2C19 and CYP2C9

• No regular concomitant (topical or systemic) medication within the last 4 weeks prior to the start of the trial

• Written informed consent given by volunteers after being provided with detailed information about the nature, risks, and scope of the clinical study as well as the expected desirable and adverse effects of the drug

• No legal incapacity and/or other circumstances rendering the subject unable to understand the nature, scope and possible consequences of the study

Exclusion Criteria:

• Known allergy or hypersensitivity against study drug or drug class

• Participation in another clinical study within the last 6 weeks prior to study

• Blood donation within the last 4 weeks prior to study

• Application of live or killed virus or bacteria vaccines within 14 days prior to study

• Alcohol or drug abuse

• Abuse of nicotine

• History of severe allergic or anaphylactic reactions to any medication

• History of or ongoing optic dysfunction (all volunteers will undergo mandatory testing at screening)

• Ongoing bacterial, viral, fungal, or atypical mycobacterial infection

• Presence of malignancy within the past 5 years, including lymphoproliferative disorders

• History of or ongoing hepatic cirrhosis regardless of cause or severity

• History of or ongoing hospital admission for cardiac disease, stroke, or pulmonary disease within the last 5 years

• History of or ongoing symptoms for blood coagulation disorders

• Seropositivity for human immunodeficiency virus (HIV), all volunteers will undergo mandatory testing at screening

• Seropositivity for hepatitis B or C virus (HepB antigen, HepC antibody), all volunteers will undergo testing at screening

• Clinically significant thrombocytopenia, bleeding disorders or a platelet count < 50,000 / µL

• WBC count < 3000/L or > 14,000/L, all volunteers will undergo mandatory testing at screening

• Hepatic enzymes (aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (AP), gamma-glutamyltranspeptidase (Gamma-GTP), lactate dehydrogenase (LDH)) and bilirubin 3 times the upper limit of normal, all volunteers will undergo mandatory testing at screening

• Serum creatinine 2 times the upper limit of normal, all volunteers will undergo mandatory testing at screening

• Abnormalities in ECG that are considered clinically relevant, all volunteers will undergo mandatory testing at screening

• Unreliability and/or lack of cooperation

• Other objections to participate in the study in the opinion of the investigator