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Effects of Tranilast on Pharmacokinetics of Methotrexate (MTX) in Patients With Rheumatoid Arthritis (RA)

NCT00717808 · Status: WITHDRAWN · Phase: PHASE1 · Type: INTERVENTIONAL

Last updated 2015-05-28

No results posted yet for this study

Summary

The treatment of rheumatoid arthritis has improved considerably in recent years with the understanding that better outcomes can be achieved by optimising the dosage schedule of conventional drugs that suppress the inflammatory response in joints. Furthermore, the development of protein based drugs that are given parenterally (i.e. by subcutaneous injection or intravenous infusion), known as biologics, have given rise to even better clinical results. However, despite this over 60% of patients with rheumatoid arthritis can still be expected to have an unacceptably high degree of disease activity and the prohibitively high cost of biologic therapy has resulted in rationing following NICE review. Therefore there is a need for more effective and less costly treatment.

The proposed study is designed to test potential drug interactions between one such candidate oral treatment, tranilast, and the gold standard therapy for rheumatoid arthritis, methotrexate, which is given as a once weekly oral, intramuscular or intradermal regimen. The drug to be tested, tranilast, an analogue of a naturally occurring molecule that regulates inflammatory responses, is currently used in the treatment of allergic inflammation and has recently been shown to be effective in an animal model of multiple sclerosis. Tranilast is an analogue of a naturally tryptophan metabolite. Laboratory studies of cell biology indicate that this molecule inhibits a number of key inflammatory pathways and the function of white blood cells that play a critical role in the inflammatory features of rheumatoid arthritis. The aim of this study is to assess whether tranilast may be useful for the treatment of RA. In an animal model of rheumatoid arthritis, initial assessment showed that prophylactic administration of tranilast interfered with the development of disease. Therapeutically, in an animal model of arthritis, tranilast was very effective, and reduced all aspects of the disease, including joint swelling, clinical score, and histological damage in a dose-dependent fashion, and reduced pain. This degree of benefit compares well with therapeutics that have been highly successful in humans, such as anti-TNF therapy. Furthermore studies at the Kennedy Institute of Rheumatology Division, Imperial College suggest that tranilast has a greater analgesic effect than the potent steroid dexamethasone at effective anti-inflammatory doses

Conditions

Interventions

DRUG

Tranilast

Tranilast (300mg twice a day) for a period of seven days whilst taking their weekly prescribed dose of methotrexate. Followed by a 7 day washout period before starting arm 2

DRUG

Placebo comparator

The patient will receive the placebo capsule twice a day whilst receiving their weekly dose of methotrexate

Sponsors & Collaborators

  • Nuon Therapeutics, Inc.

    collaborator INDUSTRY

  • Imperial College London

    lead OTHER

Principal Investigators

  • Peter C Taylor, PhD · Imperial College London

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Model
CROSSOVER

Eligibility

Min Age
18 Years
Max Age
75 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2008-09-30
Primary Completion
2009-09-30
Completion
2009-09-30

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00717808 on ClinicalTrials.gov