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

NCT ID: NCT04122560

Last Updated: 2021-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-30
• Study Completion Date: 2021-03-23

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.

Conditions

Fluconazole; Candidiasis; Invasive Fungal Infections; Obesity

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Fluconazole 200mg tab

Intervention Type: DRUG

PO dose of 400mg

Fluconazole 2 MG/ML

Intervention Type: DRUG

IV dose of 400mg

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

Group Type: ACTIVE_COMPARATOR

Fluconazole 200mg tab

Intervention Type: DRUG

PO dose of 400mg

Fluconazole 2 MG/ML

Intervention Type: DRUG

IV dose of 400mg

Interventions

Fluconazole 200mg tab

PO dose of 400mg

Intervention Type: DRUG

Fluconazole 2 MG/ML

IV dose of 400mg

Intervention Type: DRUG

Other Intervention Names

Diflucan; Diflucan

Eligibility 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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

St. Antonius Hospital

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

St. Antonius hospital

Nieuwegein, , Netherlands

Radboudumc

Nijmegen, , Netherlands

Countries

Netherlands

Other Identifiers

UMCN-AKF-18.07

Identifier Type: -

Identifier Source: org_study_id