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FOLIA: Fluconazole Pharmacokinetics, Including Bioavailability, in Obese Subjects After an Intravenous and Oral Administration

Sponsor
Radboud University Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT04122560
Collaborator
St. Antonius Hospital (Other)
25
Enrollment
2
Locations
2
Arms
15.7
Actual Duration (Months)
12.5
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The pharmacokinetics of fluconazole are expected to be different in obese patients compared to non-obese patients. The investigators will determine fluconazole and free fluconazole concentrations in 16 obese patients and 8 healthy volunteers, who will receive oral and intravenous fluconazole in a semi-simultaneous design.

A full pharmacokinetic curve will be obtained until 48 hours after intravenous administration.

Condition or Disease Intervention/Treatment Phase
  • Drug: Fluconazole 200mg tab
  • Drug: Fluconazole 2 MG/ML
 Phase 4

Detailed Description

The pharmacokinetics of fluconazole are expected to be different in obese patients compared to non-obese patients. Therefore, extrapolation of data from healthy volunteers and is not possible.

To investigate these differences 16 obese patients and 8 healthy subjects will be studied.

Patients will receive fluconazole by semi-simultaneous design. Blood sampling for pharmacokinetic analysis will be retrieved through a central venous catheter. A maximum of 100 milliliter blood in total will be drawn for this study. Patients will be monitored daily during the treatment period for adverse events of the study drug.

Full pharmacokinetic curves will be taken after oral and intravenous administration. This pharmacokinetic analysis will enable the determination of bioavailability and enable the determination of intra-individual variability.

Study Design

Study Type:
Interventional
Actual Enrollment :
25 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Comparing a 2 groups of obese subjects vs 1 group of non-obese subjectsComparing a 2 groups of obese subjects vs 1 group of non-obese subjects
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Fluconazole Pharmacokinetics, Including Bioavailability, in Obese Subjects After an Intravenous and Oral Administration (FOLIA)
Actual Study Start Date :
Nov 30, 2019
Actual Primary Completion Date :
Mar 23, 2021
Actual Study Completion Date :
Mar 23, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Obese subjects

Drug: Fluconazole tablet (diflucan) 200mg Single dose by oral administration of 400mg Drug: Fluconazole injection (diflucan) 400mg Single dose by intravenous infusion 400mg

Drug: Fluconazole 200mg tab
PO dose of 400mg
Other Names:
  • Diflucan

    • Drug: Fluconazole 2 MG/ML
    IV dose of 400mg
    Other Names:
  • Diflucan

    		•
    Active Comparator: Non-obese subjects

    Drug: Fluconazole tablet (diflucan) 200mg Single dose by oral administration of 400mg Drug: Fluconazole injection (diflucan) 400mg Single dose by intravenous infusion 400mg

    Drug: Fluconazole 200mg tab
    PO dose of 400mg
    Other Names:
  • Diflucan

    • Drug: Fluconazole 2 MG/ML
    IV dose of 400mg
    Other Names:
  • Diflucan

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Area under the plasma concentration versus time curve (AUC) of fluconazole [48 hours]

      The concentration-time curve of fluconazole will be compared with that in non-obese subjects. Exposure is assessed by area-under-the-curve from zero to 48 hours (AUC0-48h)

    Secondary Outcome Measures

    1. Area under the plasma concentration versus time curve (AUC) of fluconazole augmented dose [48 hours]

      The concentration-time curve of fluconazole will be compared with that in non-obese subjects. Exposure is assessed by area-under-the-curve from zero to 48 hours (AUC0-48h)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    1. Subjects BMI:

    2. obese groups: subject must have a BMI ≥35 kg/m2 at the time of inclusion or has undergone bariatric surgery;

    3. non-obese group: subject must have a BMI ≥18.5 and <30 kg/m2 at the time of inclusion;

    4. Subject is at least 18 of age on the day of screening and not older than 65 years of age on the day of dosing;

    5. Subject able and willing to sign the Informed Consent before screening evaluations.

    6. If a woman, is neither pregnant nor able to become pregnant and is not nursing an infant.

    For the non-obese subjects the following additional inclusion criteria applies:
    1. Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry and hematology within 6 weeks prior to study drug administration. Results of biochemistry and hematology should be within the laboratory's reference ranges (see Appendix A). If laboratory results are not within the reference ranges, the subject is included based on the investigator's judgment that the observed deviations are not clinically relevant. This should be clearly recorded.
    Exclusion Criteria:

    1. Documented history of sensitivity to fluconazole or similar azole-compound;

    2. Documented history of the long QT syndrome (LQTS);

    3. History of, or known abuse of drugs, alcohol or solvents (up until a maximum of three months before study drug administration);

    4. Use of medication that has known relevant interaction with study drug as determined by the investigator up to 1 weeks prior to study drug administration;

    5. Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks prior to study drug administration;

    6. Blood transfusion within 8 weeks prior to study drug administration;

    7. Treatment with the concerning study drug up to 7 days before administration of the study drug;

    8. Any other sound medical, psychiatric and/or social reason as determined by the investigator.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 St. Antonius hospital Nieuwegein Netherlands
    2 Radboudumc Nijmegen Netherlands

    Sponsors and Collaborators

    • Radboud University Medical Center
    • St. Antonius Hospital

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Radboud University Medical Center
    ClinicalTrials.gov Identifier:
    NCT04122560
    Other Study ID Numbers:
    • UMCN-AKF-18.07
    First Posted:
    Oct 10, 2019
    Last Update Posted:
    Jul 14, 2021
    Last Verified:
    Jul 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Radboud University Medical Center
    fluconazole
    candidiasis
    invasive fungal infections
    mycoses
    antifungal agents
    Additional relevant MeSH terms:
    Candidiasis
    Mycoses
    Invasive Fungal Infections
    Fluconazole

    Study Results

    No Results Posted as of Jul 14, 2021