Effect of Dexamethasone on CYP Enzyme Activity in Healthy Male Subjects

NCT07426042 | Not Yet Recruiting Phase 1

• 1 other identifier: Dexamethasone_cocktail
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

Purpose: The purpose of this study is to understand how dexamethasone affects the activity of drug-metabolizing enzymes in the body and how this may influence interactions with other medicines, such as voriconazole. Background: Many medicines are broken down in the body by enzymes called cytochrome P450 (CYP) enzymes. Differences in CYP enzyme activity between individuals can lead to variability in drug response and drug-drug interactions. Dexamethasone is known to affect CYP enzyme activity, and voriconazole is a medication that is metabolized by these enzymes. Participants: This study will include a total of 12 healthy adult male volunteers. Participants will be grouped based on their metabolic status, including 6 normal metabolizers (NM) and 6 poor metabolizers (PM). Interventions: Participants will receive a combination of probe drugs known as a CYP probe cocktail to assess baseline CYP enzyme activity. Dexamethasone will be administered, and the CYP probe cocktail will be given again to evaluate changes in enzyme activity. Voriconazole will be used to assess the potential for drug-drug interactions related to changes in CYP enzyme activity. Blood samples will be collected during the study. Outcome Measures: The main outcomes of this study are changes in blood concentrations of the probe drugs, which reflect changes in CYP enzyme activity, and comparisons of these changes between normal metabolizers and poor metabolizers. Hypothesis: The study hypothesizes that dexamethasone alters CYP enzyme activity and that the magnitude of this effect differs between normal metabolizers and poor metabolizers, potentially affecting the metabolism of drugs such as voriconazole.

Conditions

Drug-Drug Interactions

Outcome Measures

Primary Outcomes (3)

• Cmax of CYP Probe Substrates(Voriconazole, Midazolam, Omeprazole, Flurbiprofen)

  Cmax of CYP Probe Substrates(Voriconazole, Midazolam, Omeprazole, Flurbiprofen) will be assessed to evaluate the effects of dexamethasone on cytochrome P450 enzyme activity, specifically CYP2C9, CYP2C19, and CYP3A4, in healthy adult male subjects.

  Up to the last PK sampling time (Period 2 Day 9 for voriconazole; Period 2 Day 8 for midazolam, omeprazole, and flurbiprofen)

• AUClast of CYP Probe Substrates(Voriconazole, Midazolam, Omeprazole, Flurbiprofen)

  AUClast of CYP Probe Substrates(Voriconazole, Midazolam, Omeprazole, Flurbiprofen) will be assessed to evaluate the effects of dexamethasone on cytochrome P450 enzyme activity, specifically CYP2C9, CYP2C19, and CYP3A4, in healthy adult male subjects.

  Up to the last PK sampling time (Period 2 Day 9 for voriconazole; Period 2 Day 8 for midazolam, omeprazole, and flurbiprofen)

• AUCinf of CYP Probe Substrates(Voriconazole, Midazolam, Omeprazole, Flurbiprofen)

  AUCinf of CYP Probe Substrates(Voriconazole, Midazolam, Omeprazole, Flurbiprofen) will be assessed to evaluate the effects of dexamethasone on cytochrome P450 enzyme activity, specifically CYP2C9, CYP2C19, and CYP3A4, in healthy adult male subjects.

  Up to the last PK sampling time (Period 2 Day 9 for voriconazole; Period 2 Day 8 for midazolam, omeprazole, and flurbiprofen)

Secondary Outcomes (40)

• Tmax of Perpetrator(Dexamethasone)

  Up to the last PK sampling time (Period 2 Day 9 )

• Cmax of Perpetrator(Dexamethasone)

  Up to the last PK sampling time (Period 2 Day 9 )

• AUCtau of Perpetrator(Dexamethasone)

  Up to the last PK sampling time (Period 2 Day 9 )

• t1/2 of Perpetrator(Dexamethasone)

  Up to the last PK sampling time (Period 2 Day 9 )

• CL/F of Perpetrator(Dexamethasone)

  Up to the last PK sampling time (Period 2 Day 9 )

Study Arms (1)

Single Group

EXPERIMENTAL

A single-arm study in healthy subjects in which voriconazole, a CYP probe cocktail (caffeine, flurbiprofen, omeprazole, and midazolam), and dexamethasone are administered according to the study protocol.

Drug: Dexamethasone; Drug: CYP Probe Cocktail; Drug: voriconazole

Interventions

Dexamethasone DRUG

Dexamethasone will be administered orally to evaluate its effect on cytochrome P450 enzyme activity.

Also known as: Dexahigh Tablet

Single Group

CYP Probe Cocktail DRUG

A CYP probe cocktail composed of approved, commercially available drugs (caffeine, flurbiprofen, omeprazole, and midazolam) will be administered concomitantly as a single-dose cocktail to phenotypically assess cytochrome P450 enzyme activities before and after dexamethasone administration.

Also known as: GL Timing Tablet, Throcul Troche, OMP Tablet, Midazolam Injection

Single Group

voriconazole DRUG

Voriconazole will be administered to assess drug-drug interactions associated with changes in cytochrome P450 enzyme activity.

Also known as: Vfend Tablet

Single Group

Eligibility Criteria

• Age: 19 Years - 50 Years
• Gender Eligibility Details: Only participants who are biologically male are eligible to participate in this study.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male volunteers aged 19 to 50 years, inclusive, at the time of screening.
• Body weight between 50.0 kg and 90.0 kg, and body mass index (BMI) between 18.5 kg/m² and 29.9 kg/m² at the time of screening.
• \- BMI (kg/m²) = body weight (kg) / \[height (m)\]²
• Subjects with a CYP2C19 genotype classified as either normal metabolizers (\*1/\*1) or poor metabolizers (\*2/\*2, \*2/\*3, 3/3) based on genotyping results.
• Subjects who have received sufficient explanation of the study, fully understood the study procedures, voluntarily agreed to participate, and provided written informed consent prior to any study-related procedures.

You may not qualify if:

• Subjects with any clinically significant disease or medical history involving the hepatobiliary, renal, neurological, immunological, respiratory, gastrointestinal, endocrine, hematologic/oncologic, cardiovascular (including heart failure and Torsades de pointes), urogenital, psychiatric (including mood disorders and obsessive-compulsive disorder), or sexual dysfunction systems.
• Subjects with a history of gastrointestinal diseases (e.g., Crohn's disease, ulcer, gastritis, gastric spasm, gastroesophageal reflux disease) or gastrointestinal surgery that may affect the safety or pharmacokinetics of the investigational products, except for uncomplicated appendectomy or hernia repair.
• Subjects with known hypersensitivity or clinically significant allergic reactions to any components of the investigational products or to other drugs (e.g., aspirin, antibiotics).
• Subjects with hereditary disorders, including sucrase-isomaltase deficiency, galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
• Subjects who have received any live vaccine within 6 months prior to screening.
• Subjects with a history of active infection (including herpes simplex, herpes zoster, varicella, or systemic fungal infection) within 4 weeks prior to screening, or with evidence of ongoing infection at screening.
• Subjects without a history of varicella or measles infection and who have not been vaccinated against these diseases.
• Subjects with active or latent tuberculosis.
• Subjects with positive serologic test results for hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or syphilis.
• Subjects with a history of drug abuse or a positive urine drug screening test for drugs of abuse at screening.
• Subjects with the following vital sign abnormalities measured in the seated position after at least 3 minutes of rest at screening:
• Systolic blood pressure ≤ 90 mmHg or ≥ 150 mmHg
• Diastolic blood pressure ≤ 60 mmHg or ≥ 100 mmHg
• Subjects with a QTc interval \> 450 msec or any clinically significant abnormal cardiac rhythm on a 12-lead electrocardiogram (ECG) at screening.
• Subjects with any of the following clinically significant laboratory abnormalities at screening (including additional confirmatory tests):

Sponsors & Collaborators

• Min Kyu Park: lead

MeSH Terms

Interventions

Dexamethasone; Olfactory Marker Protein; Midazolam; Voriconazole

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Intracellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Nerve Tissue Proteins; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Soo yeon Lee

CONTACT

+82-43-269-8617; sy_lee@cbnuhctc.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Clinical Pharmacology, Chungbuk National University Hospital

Study Record Dates

• First Submitted: December 31, 2025
• First Posted: February 23, 2026
• Study Start: April 1, 2026
• Primary Completion: May 1, 2026
• Study Completion: June 1, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share