Clinical trial NCT04122560: Fluconazole Pharmacokinetics, Including Bioavailability, in Obese Subjects After an Intravenous and Oral Administration
Official title: Fluconazole Pharmacokinetics, Including Bioavailability, in Obese Subjects After an Intravenous and Oral Administration (FOLIA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fluconazole
Candidiasis
Invasive Fungal Infections
Obesity
Keywords: fluconazole
candidiasis
invasive fungal infections
mycoses
antifungal agents
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: St. Antonius Hospital
First posted: 2019-10-10
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Comparing a 2 groups of obese subjects vs 1 group of non-obese subjects
Primary purpose: TREATMENT

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.

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.

   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.

Primary outcomes:
measure: Area under the plasma concentration versus time curve (AUC) of fluconazole
timeFrame: 48 hours
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC) of fluconazole augmented dose
timeFrame: 48 hours
Other outcomes:
Locations:
city: Nieuwegein
country: Netherlands
facility: St. Antonius hospital
city: Nijmegen
country: Netherlands
facility: Radboudumc
Study officials:
References: