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

Primary Purpose

Fluconazole, Candidiasis, Invasive Fungal Infections

Status

Completed

Phase

Phase 4

Locations

Netherlands

Study Type

Interventional

Intervention

Fluconazole 200mg tab

Fluconazole 2 MG/ML

About this trial

This is an interventional treatment trial for Fluconazole focused on measuring fluconazole, candidiasis, invasive fungal infections, mycoses, antifungal agents

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Subjects BMI:
1. obese groups: subject must have a BMI ≥35 kg/m2 at the time of inclusion or has undergone bariatric surgery;
2. non-obese group: subject must have a BMI ≥18.5 and <30 kg/m2 at the time of inclusion;
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;
Subject able and willing to sign the Informed Consent before screening evaluations.
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:
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:

Documented history of sensitivity to fluconazole or similar azole-compound;
Documented history of the long QT syndrome (LQTS);
History of, or known abuse of drugs, alcohol or solvents (up until a maximum of three months before study drug administration);
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;
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;
Blood transfusion within 8 weeks prior to study drug administration;
Treatment with the concerning study drug up to 7 days before administration of the study drug;
Any other sound medical, psychiatric and/or social reason as determined by the investigator.

Sites / Locations

St. Antonius hospital
Radboudumc

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Obese subjects

Non-obese subjects

Arm Description

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

Outcomes

Primary Outcome Measures

Area under the plasma concentration versus time curve (AUC) of fluconazole

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

Area under the plasma concentration versus time curve (AUC) of fluconazole augmented dose

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)

Full Information

NCT ID

NCT04122560

First Posted

October 3, 2019

Last Updated

July 13, 2021

Sponsor

Radboud University Medical Center

Collaborators

St. Antonius Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04122560

Brief Title

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

Acronym

FOLIA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Completed

Study Start Date

November 30, 2019 (Actual)

Primary Completion Date

March 23, 2021 (Actual)

Study Completion Date

March 23, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Radboud University Medical Center

Collaborators

St. Antonius Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Fluconazole, Candidiasis, Invasive Fungal Infections, Obesity

Keywords

fluconazole, candidiasis, invasive fungal infections, mycoses, antifungal agents

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

Comparing a 2 groups of obese subjects vs 1 group of non-obese subjects

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Obese subjects

Arm Type

Experimental

Arm Description

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

Arm Title

Non-obese subjects

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Fluconazole 200mg tab

Other Intervention Name(s)

Diflucan

Intervention Description

PO dose of 400mg

Intervention Type

Drug

Intervention Name(s)

Fluconazole 2 MG/ML

Other Intervention Name(s)

Diflucan

Intervention Description

IV dose of 400mg

Primary Outcome Measure Information:

Title

Area under the plasma concentration versus time curve (AUC) of fluconazole

Description

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)

Time Frame

48 hours

Secondary Outcome Measure Information:

Title

Area under the plasma concentration versus time curve (AUC) of fluconazole augmented dose

Description

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)

Time Frame

48 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects BMI: obese groups: subject must have a BMI ≥35 kg/m2 at the time of inclusion or has undergone bariatric surgery; non-obese group: subject must have a BMI ≥18.5 and <30 kg/m2 at the time of inclusion; 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; Subject able and willing to sign the Informed Consent before screening evaluations. 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: 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: Documented history of sensitivity to fluconazole or similar azole-compound; Documented history of the long QT syndrome (LQTS); History of, or known abuse of drugs, alcohol or solvents (up until a maximum of three months before study drug administration); 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; 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; Blood transfusion within 8 weeks prior to study drug administration; Treatment with the concerning study drug up to 7 days before administration of the study drug; Any other sound medical, psychiatric and/or social reason as determined by the investigator.

Facility Information:

Facility Name

St. Antonius hospital

City

Nieuwegein

Country

Netherlands

Facility Name

Radboudumc

City

Nijmegen

Country

Netherlands

12. IPD Sharing Statement

Plan to Share IPD

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

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