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

NCT01539330 | Completed Phase 4

• 2 other identifiers: KP-VOR032008-008524-32
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Healthy

Keywords

voriconazole; microdialysis; sequence therapy; pharmacokinetics; Target Site Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics of voriconazole in plasma and interstitial space fluid of subcutaneous tissue by measuring concentrations of voriconazole in plasma and microdialysate during sequence therapy over 4 days

  Rich plasma and microdialysate sampling will be done on study day 1,3 and 4. Sparse plasma and microdialysate sampling will be done on study day 2. For characterisation of the unbound concentration-time profiles in ultrafiltered plasma and in the interstitial space fluid of subcutaneous adipose tissue (ISF) the following pharmacokinetic (PK) parameters of voriconazole will be determined by suitable PK approaches: Cmax, tmax, AUC, t1/2, CL, V after single dosing and multiple dosing (sequence therapy).

  study day 1-4

Secondary Outcomes (3)

• AUC/MIC values

  up to 1 year after study visits

• genotype analysis

  up to 10 weeks before or after study visits

• cytokine analysis

  up to 1 year after study visits

Interventions

Voriconazole DRUG

At beginning of study visit 1 (0-12 h): 6 mg/kg, IV (in the vein) over a period of 120 min at beginning of study visit 2 (12-24 h): 6 mg/kg, IV (in the vein) over a period of 120 min at beginning of study visit 3 (24-36 h): 4 mg/kg, IV (in the vein) over a period of 80 min at beginning of study visit 4 (36-48 h): 4 mg/kg, IV (in the vein) over a period of 80 min at beginning of study visit 5 (48-60 h), 6 (60-72 h) and 7 (72-84 h): 200 mg po

Also known as: VFEND® Pfizer

microdialysis OTHER

long-term microdialysis over study days 1-4 (visits 1-7)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Martin-Luther-Universität Halle-Wittenberg: lead
• Medical University of Vienna: collaborator

Study Sites (1)

Medical University of Vienna, Department of Clinical Pharmacology

Vienna, 1090, Austria

Location

Related Publications (2)

• Simmel F, Kloft C. Microdialysis feasibility investigations with the non-hydrophilic antifungal voriconazole for potential applications in nonclinical and clinical settings. Int J Clin Pharmacol Ther. 2010 Nov;48(11):695-704. doi: 10.5414/cpp48695.

  PMID: 20979927 BACKGROUND

• Simmel F, Kirbs C, Erdogan Z, Lackner E, Zeitlinger M, Kloft C. Pilot investigation on long-term subcutaneous microdialysis: proof of principle in humans. AAPS J. 2013 Jan;15(1):95-103. doi: 10.1208/s12248-012-9412-z. Epub 2012 Oct 13.

  PMID: 23065438 RESULT

MeSH Terms

Interventions

Voriconazole; Microdialysis

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dialysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Markus Müller, Prof. Dr.

  Medical University of Vienna, Department of Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Department of Clinical Pharmacy

Study Record Dates

• First Submitted: February 9, 2012
• First Posted: February 27, 2012
• Study Start: February 1, 2009
• Primary Completion: February 1, 2013
• Study Completion: August 1, 2013
• Last Updated: November 1, 2013

Record last verified: 2013-10

Locations

AU (1)