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

• ClinicalTrials.gov Identifier: NCT04122560
• Recruitment Status: Not yet recruiting
• First Posted: October 10, 2019
• Last Update Posted: October 10, 2019
• Sponsor: Radboud University
• Collaborator: St. Antonius Hospital
• Information provided by (Responsible Party): Radboud University

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
Fluconazole; Candidiasis; Invasive Fungal Infections; Obesity	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 (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Comparing 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)
• Estimated Study Start Date: November 1, 2019
• Estimated Primary Completion Date: August 1, 2020
• Estimated Study Completion Date: December 1, 2020

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 Name: Diflucan; Drug: Fluconazole 2 MG/ML; IV dose of 400mg; Other Name: 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 Name: Diflucan; Drug: Fluconazole 2 MG/ML; IV dose of 400mg; Other Name: Diflucan

Outcome Measures

Primary Outcome Measures :

1. Area under the plasma concentration versus time curve (AUC) of fluconazole [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Netherlands

St. Antonius hospital

Nieuwegein, Netherlands

Radboudumc; Not yet recruiting

Nijmegen, Netherlands

Contact: Angela Colbers, PhD 0243616405

Sponsors and Collaborators

Radboud University

St. Antonius Hospital

More Information

• Responsible Party: Radboud University
• ClinicalTrials.gov Identifier: NCT04122560 History of Changes
• Other Study ID Numbers: UMCN-AKF-18.07
• First Posted: October 10, 2019
• Last Update Posted: October 10, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• 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:

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

Additional relevant MeSH terms:

Candidiasis; Mycoses; Invasive Fungal Infections; Fluconazole; Antifungal Agents; Anti-Infective Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors