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

NCT07196449 | Active Not Recruiting Phase 1

• 1 other identifier: MRCI
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Drug Drug Interaction (DDI)

Keywords

MRCI; Methotrexate; Rifampicin; Cyclosporine; DDI; Drug Drug Interaction

Outcome Measures

Primary Outcomes (2)

• MTX Cmax

  Peack plasma concentration (Cmax) of methotrexate

  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)

• MTX AUClast

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

  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)

• MTX AUCinf

  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)

• MTX Tmax

  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)

• MTX t1/2

  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)

• MTX CL/F

  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)

• MTX Vz/F

  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)

Study Arms (6)

Group 1

EXPERIMENTAL

Sequence 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).

Drug: Methotrexate; Drug: Rifampicin; Drug: Cyclosporine

Group 2

EXPERIMENTAL

Sequence 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).

Drug: Methotrexate; Drug: Rifampicin; Drug: Cyclosporine

Group 3

EXPERIMENTAL

Sequence 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.

Drug: Methotrexate; Drug: Rifampicin; Drug: Cyclosporine

Group 4

EXPERIMENTAL

Sequence 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.

Drug: Methotrexate; Drug: Rifampicin; Drug: Cyclosporine

Group 5

EXPERIMENTAL

Sequence 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.

Drug: Methotrexate; Drug: Rifampicin; Drug: Cyclosporine

Group 6

EXPERIMENTAL

Sequence 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.

Drug: Methotrexate; Drug: Rifampicin; Drug: Cyclosporine

Interventions

Methotrexate DRUG

Methotrexate Tab. 2.5 mg (Korea United Pharm)

Also known as: MTX

Group 1; Group 2; Group 3; Group 4; Group 5; Group 6

Rifampicin DRUG

Rifampin Cap. 150 mg (Yuhan Corporation)

Also known as: RFP

Group 1; Group 2; Group 3; Group 4; Group 5; Group 6

Cyclosporine DRUG

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

Also known as: CsA

Group 1; Group 2; Group 3; Group 4; Group 5; Group 6

Eligibility Criteria

• Age: 19 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Seoul National University Bundang Hospital: lead

Study Sites (1)

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13605, South Korea

Location

MeSH Terms

Interventions

Methotrexate; Rifampin; Cyclosporine

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Cyclosporins; Peptides, Cyclic; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Jae Yong Chung, Professor

  Seoul National University Bundang Hospital, Department of Cliniacl Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Open-label, randomized, 3-period, 6-sequence crossover Phase 1 clinical trial in healthy volunteers

Study Record Dates

• First Submitted: May 20, 2025
• First Posted: September 29, 2025
• Study Start: May 14, 2025
• Primary Completion: June 9, 2025
• Study Completion: April 14, 2026
• Last Updated: September 29, 2025

Record last verified: 2025-09

Locations

KR (1)