Flucloxacillin as an Inducer of CYP-enzymes

NCT ID: NCT04840641

Last Updated: 2022-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-25
• Study Completion Date: 2021-12-28

Brief Summary

Worldwide there is an increase in antibiotic resistance which may have potential fatal long-term consequences. This is due to extensive use and sometimes misuse of antibiotics in the treatment of harmless infections.

The aim of this study is to investigate if treatment with flucloxacillin increases drug metabolism in healthy volunteers through induction of cytochrome P450 (CYP) enzymes, CYP1A4, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4.

The hypothesis is based on an in vitro study showing that flucloxacillin activates a receptor (PXR) responsible for transcription of CYP enzymes.

Trial subjects will ingest flucloxacillin for 31 days and at day 10 and 28 ingest a cocktail of 6 drugs to determine if the CYP enzymes have been induced. Plasma and urine will be drawn over 72 hours to determine the concentration of the 6 drugs and their metabolites.

Change in flucloxacillin concentration will also be measured at day 9 and 27 to establish if flucloxacillin induces its own metabolism.

Conditions

Healthy Volunteers; Drug Drug Interaction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Baseline

The investigators measure the baseline of flucloxacillin and cocktaildrugs.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Flucloxacillin treatment

The investigators measure the concentration of flucloxacillin after 9 and 27 days and the concentration of cocktaildrugs after 10 and 28 days.

Group Type: EXPERIMENTAL

Flucloxacillin

Intervention Type: DRUG

Healthy volunteers will take 2x500 mg flucloxacillin 3 times a day for 31 days. The investigators will measure the baseline concentration of the 6-cocktaildrugs and flucloxacillin before start of 31 days of flucloxacillin treatment. On day 9 and 27 the investigators will measure the concentration of flucloxacillin. On day 10 and 28 the investigators will measure the concentration of the 6 cocktaildrugs

Interventions

Flucloxacillin

Healthy volunteers will take 2x500 mg flucloxacillin 3 times a day for 31 days. The investigators will measure the baseline concentration of the 6-cocktaildrugs and flucloxacillin before start of 31 days of flucloxacillin treatment. On day 9 and 27 the investigators will measure the concentration of flucloxacillin. On day 10 and 28 the investigators will measure the concentration of the 6 cocktaildrugs

Intervention Type: DRUG

Other Intervention Names

Caffeine; Efavirenz; Losartan; Omeprazole; Metoprolol; Midazolam

Eligibility Criteria

Inclusion Criteria

• Age 18-55 years
• The following data have to be in the normal range or only clinical insignificantly different from this: eGFR, ALAT, bilirubin, HbA1c, haemoglobin
• BMI 18.5 - 29.9 kg m-2
• Non-smoker (abstained from smoking minimum 2 weeks before the first study day and during the trial)
• Generally healthy
• Willing to give informed consent

Exclusion Criteria

• Known sensitivity to any of the used drugs or any excipients listed in section 6.1 in the Summary of Product Characteristics (SmPC).
• Known allergy towards penicillin or cephalosporines
• Any of the following diseases (current or previous):

Heart disease, known family history of prolonged QTc interval, sudden death or conditions that might prolonged QTc-intervals, hypotension, severe disturbance of electrolyte balance e.g. hypokalemia or hypomagnesemia, myasthenia gravis, lung- or respiratory diseases, an anatomically abnormality of the respiratory tract, sleep apnea syndrome

• Intake of any significant prescription drugs, over-the- counter drugs, herbal drugs or dietary supplements. Contraindicated drugs include: Benzodiazepines, beta blockers, ergot alkaloids, herbal preparations containing St. John's wort, antiarrhythmics, neuroleptics, antidepressive agents, antibiotics, antifungal agents, non-sedating antihistamines, antimalarials, methadone, elbasvir, grazoprevir, nelfinavir cisapride, pimozide, bepridil

• Alcohol abuse or if the Danish Health Authority recommendation regarding alcohol intake has been exceeded 2 weeks before the first study day (men 14 units alcohol/week, women 7 units alcohol/week)
• Women who are breastfeeding
• Positive pregnancy test at inclusion screening or at any of the study days
• Participation in any other interventional trials

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

SignaTope GmbH, Germany

UNKNOWN

Sponsor Role: collaborator

University of Southern Denmark

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Southern Denmark

Odense, Region Syddanmark, Denmark

Countries

Denmark

Other Identifiers

2020-004044-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AKF-396

Identifier Type: -

Identifier Source: org_study_id