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Drug Drug Interaction (DDI)Phase 1MRCINCT07196449

Drug-Drug Interaction of Rifampicin and Cyclosporine on Methotrexate Pharmacokinetics in Healthy Subjects

A Phase 1 study testing Methotrexate, Rifampicin and Cyclosporine in people with Drug Drug Interaction (DDI), run by Seoul National University Bundang Hospital at 1 site in South Korea.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This study will evaluate how methotrexate is processed in the body when given with low doses of rifampicin or cyclosporine. These drugs may affect how methotrexate is absorbed and cleared, which could change its safety and effectiveness. Read more about this study

Who is it for?
Ages 19 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for
Drug Drug Interaction (DDI)
What is being tested?
Methotrexate, Rifampicin and Cyclosporine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteSouth Korea
Study dates
14 May 2025to 14 Apr 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 to 45 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy adult male volunteers aged between 19 and 45 years (inclusive) at the time of screening visit.
  • Body weight between 50.0 kg and 90.0 kg (inclusive) and a body mass index (BMI) between 18.0 and 30.0 kg/m² (inclusive) at the time of screening.
  • ※ BMI (Body Mass Index) = weight (kg) / height² (m²)
  • Judged by the investigator to be suitable for participation in the study based on physical examination, clinical laboratory tests, and medical history.
  • Willingly provided written informed consent to participate after receiving and fully understanding a detailed explanation of the study prior to any screening procedures.

Who cannot join

  • Individuals with clinically significant hepatic (e.g., biliary obstruction), renal, neurologic, immunologic, gastrointestinal (e.g., irritable bowel syndrome, constipation), respiratory, endocrine disorders, or hematologic/oncologic, cardiovascular, or psychiatric disorders (e.g., mood disorders, obsessive-compulsive disorder), or relevant medical history.
  • History of clinically significant hypersensitivity to the investigational product, drugs in the same class, or other medications (e.g., aspirin, antibiotics) or food products.
  • History of gastrointestinal diseases (e.g., Crohn's disease, peptic ulcer) or surgeries that may affect drug absorption (except for simple appendectomy or hernia repair).
  • Known hereditary problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
  • Subjects meeting any of the following criteria at screening: AST(SGOT) or ALT(SGPT) > 1.5 × upper limit of normal (ULN); eGFR < 80 mL/min/1.73m² (calculated using CKD-EPI equation); QTc interval > 450 ms; Sitting blood pressure after ≥3 minutes of rest: systolic < 90 mmHg or > 150 mmHg, or diastolic < 50 mmHg or > 100 mmHg.
  • Total bilirubin > 1.8 mg/dL or serum potassium > 5.0 mmol/L (risk of hyperkalemia).
Show all 19Show fewer
  • Positive results for HBsAg, anti-HCV, HIV (Ag/Ab), or RPR serologic tests.
  • History of drug abuse or positive results for drugs of abuse in urine screening.
  • Habitual alcohol consumption > 21 units/week (1 unit = 10 g pure alcohol), or unable to abstain from alcohol during the study.
  • Current smokers or those unable to abstain from smoking from 3 months prior to first dosing until the end of the study.
  • Use of enzyme or transporter inducers/inhibitors (e.g., barbiturates, statins, digoxin) within 3 months prior to the first dosing.
  • Unable to avoid St. John's Wort or grapefruit-containing products from 14 days before first dosing until study completion.
  • Habitual excessive caffeine intake (>5 units/day), or unable to abstain from caffeine or caffeine-containing products (e.g., coffee, tea, energy drinks) from 7 days before first dosing through the study.
  • Use of prescription drugs or herbal medicines within 2 weeks, or over-the-counter drugs, supplements, or vitamins within 10 days before first dosing (unless deemed acceptable by the investigator).
  • Participation in another clinical trial involving drug administration within 6 months prior to the first dosing day.
  • Whole blood donation within 2 months or component donation or transfusion within 1 month prior to the first dosing day.
  • Individuals with unusual dietary habits (e.g., strict vegetarians) or those unable to consume the provided meals entirely.
  • Individuals (male or female) of childbearing potential who are unable or unwilling to use acceptable contraception (e.g., surgical sterilization of self or partner, intrauterine device, hormonal contraception, diaphragm/condom with spermicide) during the study and for 2 weeks after the last dose of investigational product.
  • Any other condition that the investigator deems makes the subject unsuitable for study participation.

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Seoul National University Bundang Hospital

    Seongnam-si, Gyeonggi-do, 13605

Other trials in South Korea

About this study

Official title: A Drug-drug Interaction Study to Evaluate the Effect of Rifampicin and Cyclosporine on the Pharmacokinetics of Methotrexate in Healthy Subjects

This study will evaluate how methotrexate is processed in the body when given with low doses of rifampicin or cyclosporine. These drugs may affect how methotrexate is absorbed and cleared, which could change its safety and effectiveness. Healthy volunteers will receive methotrexate with either rifampicin or cyclosporine, and blood samples will be collected to measure drug levels. The findings may help identify possible drug interactions and improve the safe use of methotrexate.

Read the detailed description

Unexpected or unrecognized drug-drug interactions can reduce efficacy, cause toxicity, or even lead to fatal outcomes. Inhibition or induction of drug transporters involved in hepatic or renal uptake/efflux may alter drug exposure, affecting safety and efficacy. The FDA requires clinically significant interactions to be assessed prior to approval.

OATPs (primarily hepatic uptake) and BCRP (hepatic and renal efflux) share many substrates, but their combined inhibition has not been well studied in humans. Methotrexate, a substrate of both OATP and BCRP, is widely used at varying doses for cancer, psoriasis, and rheumatoid arthritis, often in combination with other drugs such as NSAIDs, which may result in interactions requiring close monitoring.

Rifampicin, an antibiotic, inhibits OATP1B1/1B3 in a dose-dependent manner, while cyclosporine, an immunosuppressant, inhibits OATP and BCRP. In our previous study (IRB No. B-2110-715-001), the investigators quantitatively demonstrated that rifampicin reduces 7-OH-methotrexate formation via OATP inhibition. However, dose-dependent inhibition by rifampicin and the impact of cyclosporine on methotrexate pharmacokinetics remain unclear.

This study aims to evaluate the pharmacokinetics of methotrexate following co-administration with low-dose rifampicin (150 or 300 mg) and cyclosporine in healthy volunteers. The investigators will also explore the role of methotrexate metabolites as potential biomarkers to assess OATP-mediated interactions.

Being tested
Methotrexate, Rifampicin, Cyclosporine
Keywords
MRCI, Methotrexate, Rifampicin, Cyclosporine, DDI, Drug Drug Interaction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MethotrexateDrug

    Also called MTX

    Methotrexate Tab. 2.5 mg (Korea United Pharm)

  • RifampicinDrug

    Also called RFP

    Rifampin Cap. 150 mg (Yuhan Corporation)

  • CyclosporineDrug

    Also called CsA

    Cypol-N Cap. 100 mg (Chong Kun Dang)

Study groups in NCT07196449
Study groupRoleWhat they receive
Group 1ExperimentalSequence Group 1: Two subjects assigned to this group will receive Methotrexate 2.5 mg + Rifampicin 150 mg (single co-administration) in Period 1, Methotrexate 2.5 mg + Rifampicin 300 mg (single co-administration) in Period 2, and Methotrexate 2.5 mg + Cyclosporine 100 mg in Period 3 (1 subject with simultaneous administration, 1 subject with 1-hour staggered administration).
Receives: Drug: Methotrexate; Drug: Rifampicin; Drug: Cyclosporine
Group 2ExperimentalSequence Group 2: Two subjects assigned to this group will receive Methotrexate 2.5 mg + Rifampicin 300 mg (single co-administration) in Period 1, Methotrexate 2.5 mg + Rifampicin 150 mg (single co-administration) in Period 2, and Methotrexate 2.5 mg + Cyclosporine 100 mg in Period 3 (1 subject with simultaneous administration, 1 subject with 1-hour staggered administration).
Receives: Drug: Methotrexate; Drug: Rifampicin; Drug: Cyclosporine
Group 3ExperimentalSequence Group 3: Two subjects assigned to this group will receive Methotrexate 2.5 mg + Rifampicin 300 mg (single co-administration) in Period 1, Methotrexate 2.5 mg + Cyclosporine 100 mg in Period 2 (1 subject with simultaneous administration, 1 subject with 1-hour staggered administration), and Methotrexate 2.5 mg + Rifampicin 150 mg (single co-administration) in Period 3.
Receives: Drug: Methotrexate; Drug: Rifampicin; Drug: Cyclosporine
Group 4ExperimentalSequence Group 4: Two subjects assigned to this group will receive Methotrexate 2.5 mg + Rifampicin 150 mg (single co-administration) in Period 1, Methotrexate 2.5 mg + Cyclosporine 100 mg in Period 2 (1 subject with simultaneous administration, 1 subject with 1-hour staggered administration), and Methotrexate 2.5 mg + Rifampicin 300 mg (single co-administration) in Period 3.
Receives: Drug: Methotrexate; Drug: Rifampicin; Drug: Cyclosporine
Group 5ExperimentalSequence Group 5: Two subjects assigned to this group will receive Methotrexate 2.5 mg + Cyclosporine 100 mg in Period 1 (1 subject with simultaneous administration, 1 subject with 1-hour staggered administration), Methotrexate 2.5 mg + Rifampicin 150 mg (single co-administration) in Period 2, and Methotrexate 2.5 mg + Rifampicin 300 mg (single co-administration) in Period 3.
Receives: Drug: Methotrexate; Drug: Rifampicin; Drug: Cyclosporine
Group 6ExperimentalSequence Group 6: Two subjects assigned to this group will receive Methotrexate 2.5 mg + Cyclosporine 100 mg in Period 1 (1 subject with simultaneous administration, 1 subject with 1-hour staggered administration), Methotrexate 2.5 mg + Rifampicin 300 mg (single co-administration) in Period 2, and Methotrexate 2.5 mg + Rifampicin 150 mg (single co-administration) in Period 3.
Receives: Drug: Methotrexate; Drug: Rifampicin; Drug: Cyclosporine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTX Cmax

    Peack plasma concentration (Cmax) of methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  2. MTX AUClast

    Area under the concentration-time curve to last measurable concentration (AUClast) of methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

Secondary outcomes (17)

  1. MTX AUCinf

    Area under the plasma concentration-time curve from time zero to infinity (AUCinf) of Methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  2. MTX Tmax

    Time to maximum plasma concentration (Tmax) of methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  3. MTX t1/2

    Terminal elimination half-life (t1/2) of methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  4. MTX CL/F

    Apparent clearance (CL/F) of methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  5. MTX Vz/F

    Apparent volume of distribution (Vz/F) of methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  6. MTX fe

    Fraction of dose excreted unchanged in urine (fe) of methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  7. MTX CLR

    Renal clearance (CLR) of methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  8. 7-OH MTX Cmax

    Maximum plasma concentration (Cmax) of 7-hydroxy methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  9. 7-OH MTX AUClast

    Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUClast) of 7-hydroxy methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  10. 7-OH MTX AUCinf

    Area under the plasma concentration-time curve from time zero to infinity (AUCinf) of 7-hydroxy methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  11. 7-OH MTX Tmax

    Time to maximum plasma concentration (Tmax) of 7-hydroxy methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  12. 7-OH MTX t1/2

    Terminal elimination half-life (t1/2) of 7-hydroxy methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  13. 7-OH MTX CL/F

    Apparent clearance (CL/F) of 7-hydroxy methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  14. 7-OH MTX Vz/F

    Apparent volume of distribution (Vz/F) of 7-hydroxy methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  15. 7-OH MTX fe

    Fraction of dose excreted unchanged in urine (fe) of 7-hydroxy methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  16. 7-OH MTX CLR

    Renal clearance (CLR) of 7-hydroxy methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

  17. 7-OH MTX MR

    Metabolic ratio (MR) of 7-hydroxy methotrexate

    Measured: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Sep 2025
  2. Study start14 May 2025
  3. Primary completion9 Jun 2025
  4. Study completion14 Apr 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Crossover
Model description
Open-label, randomized, 3-period, 6-sequence crossover Phase 1 clinical trial in healthy volunteers
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07196449
Sponsor's protocol ID
MRCI
Acronym
MRCI
Status last verified
Sep 2025
First submitted
20 May 2025
Last updated
29 Sep 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Methotrexate, Rifampicin and Cyclosporine in people with Drug Drug Interaction (DDI), run by Seoul National University Bundang Hospital at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 29 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTX Cmax (time frame: pre-dose (0 hours), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose for each period (11 time points per period)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07196449.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2025.

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