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

Sponsor
Seoul National University Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT05575297
Collaborator
(none)
12
Enrollment
1
Location
4
Arms
4.6
Actual Duration (Months)
2.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Drug: Methotrexate Sodium
  • Drug: Rifampicin Sodium
  • Drug: Febuxostat Tablets
 Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
12 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
A Drug-drug Interaction Study to Evaluate the Effect of Rifampicin and Febuxostat on the Pharmacokinetics of Methotrexate in Healthy Subjects
Actual Study Start Date :
Dec 20, 2021
Actual Primary Completion Date :
May 3, 2022
Actual Study Completion Date :
May 9, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Methotrexate

Drug: Methotrexate Sodium
Methotrexate oral administration alone
Experimental: Methotrexate + Rifampicin

Methotrexate + Rifampicin

Drug: Methotrexate Sodium
Methotrexate oral administration alone

Drug: Rifampicin Sodium
Co-administration of methotrexate and rifampicin
Experimental: Methotrexate + Febuxostat

Methotrexate + Febuxostat

Drug: Methotrexate Sodium
Methotrexate oral administration alone

Drug: Febuxostat Tablets
Co-administration of methotrexate and febuxostat
Experimental: Methotrexate + Rifampicin + Febuxostat

Methotrexate + Rifampicin + Febuxostat

Drug: Methotrexate Sodium
Methotrexate oral administration alone

Drug: Rifampicin Sodium
Co-administration of methotrexate and rifampicin

Drug: Febuxostat Tablets
Co-administration of methotrexate and febuxostat

Outcome Measures

Primary Outcome Measures

  1. 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

  2. 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

  3. 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

  1. 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

  2. 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

  3. 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

Eligibility Criteria

Criteria

Ages Eligible for Study:
19 Years to 45 Years
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
Yes
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Seoul National University Bundang Hospital Seoul Korea, Republic of

Sponsors and Collaborators

  • Seoul National University Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Jae Yong Chung, MD, PhD, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT05575297
Other Study ID Numbers:
  • MRFI
First Posted:
Oct 12, 2022
Last Update Posted:
Oct 12, 2022
Last Verified:
Oct 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Rifampin
Methotrexate
Febuxostat

Study Results

No Results Posted as of Oct 12, 2022