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

Drug Interaction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05575297
• Other study ID #: MRFI
• Status: Completed
• Phase: Phase 1
• Start date: December 20, 2021
• Est. completion date: May 9, 2022

Study information

• Verified date: October 2022
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 9, 2022
• Est. primary completion date: May 3, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 19 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Drug Interaction

Intervention

Drug:
• Methotrexate Sodium
Methotrexate oral administration alone
• Rifampicin Sodium
Co-administration of methotrexate and rifampicin
• Febuxostat Tablets
Co-administration of methotrexate and febuxostat

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Bundang Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare Cmax of methotrexate	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	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)
Primary	Compare AUClast of methotrexate	Compare the area under the plasma concentration-time curve to from 0 to last measurable time point (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)
Primary	Compare AUCinf of methotrexate	Compare area under the plasma concentration-time curve from 0 hours to infinite time (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)
Secondary	Compare Cmax of 7-hydroxy methotrexate	Compare the maximum concentration (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)
Secondary	Compare AUClast of 7-hydroxy methotrexate	Compare area under the plasma concentration-time curve to last measurable time point (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)
Secondary	Compare AUCinf of 7-hydroxy methotrexate	Compare area under the plasma concentration-time curve from 0 hours to infinite time (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)