A Drug-drug Interaction Study to Evaluate the Effect of Rifampicin and Febuxostat on the Pharmacokinetics of Methotrexate in Healthy Subjects

Phase 1

Completed

• Conditions: Drug Interaction
• Interventions: Drug: Methotrexate Sodium; Drug: Rifampicin Sodium; Drug: Febuxostat Tablets

• Registration Number: NCT05575297
• Lead Sponsor: Seoul National University Hospital

Brief Summary

To investigate the effect of rifampicin and febuxostat on pharmacokinetics of methotrexate in healthy volunteers

Detailed Description

Not available

Study Timeline

• Study Start: 2021-12-20
• Primary Completion: 2022-05-03
• Study Completion: 2022-05-09
• Status Verified: 2022-10
• Study First Submitted: 2022-10-04
• Study First Submitted QC: 2022-10-10
• Last Update Submitted: 2022-10-10
• Study First Posted: 2022-10-12
• Last Update Posted: 2022-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 12

Inclusion Criteria

• Age between 19 to 50, healthy male subjects (at screening)
• Body weight between 50.0 kg - 90.0 kg, BMI between 18.0 - 30.0 kg/m2
• Subject who totally understand the progress of this clinical trials, make decision by his free will, and signed a consent form to follow the progress

Exclusion Criteria

• Subject who has a past or present history of any diseases (eg. liver, kidney, neurology, immunology, pulmonary, endocrine, hematology, oncology, cardiology, mental disorder)
• Subject who had GI tract disease (Crohn's disease, ulcer, acute or chronic pancreatitis) or surgery (appendectomy, hernioplasty are excluded)
• Serum AST(SGOT), ALT(SGPT), total bilirubin >1.5 times upper limit of normal range, MDRD eGFR < 60mL/min/1.73m2, WBC count < 3,500 /uL, SBP < 90 mmHg or > 150 mmHg, DBP < 50 mmHg or >100 mmHg
• Subject who had galactose intolerance, Lapplactase deficiency or glucose-galactose malabsorption
• Subject who had received drugs inhibiting or inducing metabolic enzymes/transporters such as barbiturates, statins, digoxin in 3 months
• Subject who had taken St.John's wort and food including grapefruit in 2 weeks
• Smoking in 3 months
• Subject who had whole blood donation in 2 months, or component blood donation in 1 month or transfusion in 1 month currently

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Methotrexate + Rifampicin	Methotrexate Sodium	Methotrexate + Rifampicin
Methotrexate + Febuxostat	Methotrexate Sodium	Methotrexate + Febuxostat
Methotrexate	Methotrexate Sodium	-
Methotrexate + Rifampicin	Rifampicin Sodium	Methotrexate + Rifampicin
Methotrexate + Febuxostat	Febuxostat Tablets	Methotrexate + Febuxostat
Methotrexate + Rifampicin + Febuxostat	Methotrexate Sodium	Methotrexate + Rifampicin + Febuxostat
Methotrexate + Rifampicin + Febuxostat	Febuxostat Tablets	Methotrexate + Rifampicin + Febuxostat
Methotrexate + Rifampicin + Febuxostat	Rifampicin Sodium	Methotrexate + Rifampicin + Febuxostat

Primary Outcome Measures

Name	Time	Method
Compare Cmax of methotrexate	pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1)	Compare the maximum concentration (Cmax), area under the plasma concentration-time curve to last measurable time point (AUClast) and area under the plasma concentration-time curve from 0 hours to infinite time (AUCinf) of methotrexate
Compare AUClast of methotrexate	pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1)	Compare the area under the plasma concentration-time curve to from 0 to last measurable time point (AUClast) of methotrexate
Compare AUCinf of methotrexate	pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1)	Compare area under the plasma concentration-time curve from 0 hours to infinite time (AUCinf) of methotrexate

Secondary Outcome Measures

Name	Time	Method
Compare Cmax of 7-hydroxy methotrexate	pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1)	Compare the maximum concentration (Cmax) of 7-hydroxy methotrexate
Compare AUClast of 7-hydroxy methotrexate	pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1)	Compare area under the plasma concentration-time curve to last measurable time point (AUClast) of 7-hydroxy methotrexate
Compare AUCinf of 7-hydroxy methotrexate	pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1)	Compare area under the plasma concentration-time curve from 0 hours to infinite time (AUCinf) of 7-hydroxy methotrexate

Trial Locations

Locations (1)

Seoul National University Bundang Hospital; 🇰🇷 Seoul, Korea, Republic of