None listed
Conditions
Interventions
Drug : - This is an open-label, crossover Phase 1 clinical trial designed to evaluate the pharmacokinetics of methotrexate when co-administered with low-dose rifampicin (100 mg, 150 mg) or cyclosporin
Sponsors
Seoul National University Bundang Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Healthy adult male volunteers aged between 19 and 45 years (inclusive) at the time of screening visit. 2) 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) 3) Judged by the investigator to be suitable for participation in the study based on physical examination, clinical laboratory tests, and medical history. 4) Willingly provided written informed consent to participate after receiving and fully understanding a detailed explanation of the study prior to any screening procedures.
Exclusion criteria
Exclusion criteria: 1) 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. 2) History of clinically significant hypersensitivity to the investigational product, drugs in the same class, or other medications (e.g., aspirin, antibiotics) or food products. 3) 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). 4) Known hereditary problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. 5) Subjects meeting any of the following criteria at screening: Aspartate aminotransferase or Alanine aminotransferase greater than 1.5 times the upper limit of normal; estimated glomerular filtration rate less than 80 mL/min/1.73m² (calculated using Chronic Kidney Disease Epidemiology Collaboration equation); corrected QT interval greater than 450 milliseconds; sitting blood pressure after at least 3 minutes of rest: systolic blood pressure less than 90 mmHg or greater than 150 mmHg, or diastolic blood pressure less than 50 mmHg or greater than 100 mmHg. 6) Total bilirubin > 1.8 mg/dL or serum potassium > 5.0 mmol/L (risk of hyperkalemia). 7) Positive results for hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antigen/antibody, or rapid plasma reagin serologic tests. 8) History of drug abuse or positive results for drugs of abuse in urine screening. 9) Habitual alcohol consumption > 21 units/week (1 unit = 10 g pure alcohol), or unable to abstain from alcohol during the study. 10) Current smokers or those unable to abstain from smoking from 3 months prior to first dosing until the end of the study. 11) Use of enzyme or transporter inducers/inhibitors (e.g., barbiturates, statins, digoxin) within 3 months prior to the first dosing. 12) Unable to avoid St. John’s Wort or grapefruit-containing products from 14 days before first dosing until study completion. 13) 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. 14) 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). 15) Participation in another clinical trial involving drug administration within 6 months prior to the first dosing day. 16) Whole blood donation within 2 months or component donation or transfusion within 1 month prior to the first dosing day. 17) Individuals with unusual dietary habits (e.g., strict vegetarians) or those unable to consume the provided meals entirely. 18) 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. 19) Any other condition that the investigator deems makes the subject unsuitable for study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum concentration of methotrexate;Area under the curve from time zero to the last measurable concentration of methotrexate | — |
Secondary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration–time curve extrapolated to infinity of methotrexate;Time to reach maximum plasma concentration of methotrexate;Terminal elimination half-life of methotrexate;Apparent total clearance of methotrexate;Apparent volume of distribution of methotrexate;Fraction of dose excreted unchanged in urine of methotrexate;Renal clearance of methotrexate;Maximum plasma concentration of 7-hydroxy methotrexate;Area under the plasma concentration–time curve to the last measurable concentration of 7-hydroxy methotrexate;Area under the plasma concentration–time curve extrapolated to infinity of 7-hydroxy methotrexate;Time to reach maximum plasma concentration of 7-hydroxy methotrexate;Terminal elimination half-life of 7-hydroxy methotrexate;Apparent total clearance of 7-hydroxy methotrexate;Apparent volume of distribution of 7-hydroxy methotrexate;Fraction of dose excreted unchanged in urine of 7-hydroxy methotrexate;Renal clearance of 7-hydroxy methotrexate;Metabolic ratio of 7-hydroxy methotrexate | — |
Countries
Korea, Republic of
Contacts
Public ContactHyun Joon Lee
Seoul National University Bundang Hospital
Outcome results
None listed