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

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Candidiasis; Invasive Fungal Infections; Fluconazole
• Intervention / Treatment: Drug: Fluconazole 200mg tab; Drug: Fluconazole 2 MG/ML

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 Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Nieuwegein, Netherlands
    • St. Antonius Hospital
  • Nijmegen, Netherlands
    • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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;
2. 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;
3. Subject able and willing to sign the Informed Consent before screening evaluations.

4. 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:

5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	48 hours

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: St. Antonius Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 30, 2019
• Primary Completion (ACTUAL): March 23, 2021
• Study Completion (ACTUAL): March 23, 2021

Study Registration Dates

• First Submitted: October 3, 2019
• First Submitted That Met QC Criteria: October 9, 2019
• First Posted (ACTUAL): October 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 14, 2021
• Last Update Submitted That Met QC Criteria: July 13, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: candidiasis; invasive fungal infections; fluconazole; mycoses; antifungal agents
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Candidiasis; Mycoses; Invasive Fungal Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole
• Other Study ID Numbers: UMCN-AKF-18.07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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