Patients with active rheumatoid arthritis who are on a stable dose of methotrexate
Conditions
Interventions
Trade Name: Ribazen
Product Name: Tranilast
Pharmaceutical Form: Tablet
INN or Proposed INN: Tranilast
CAS Number: 53902-12-8
Current Sponsor code: None
Concentration unit: mg milligram(s)
Concentrat
Sponsors
Nuon Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria 1. Signed and dated written Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent obtained from the subject in accordance with the local regulations; 2. Male or female subjects, =18 to =75 years of age, who have a diagnosis of RA (using the American Rheumatism Association 1987 Revised Criteria for at least 6 months prior to screening, and are Functional Class 1-3 (as defined by the 1991 Revised Criteria for the Classification of Global Functional Status in Rheumatoid Arthritis at baseline; 3. Subjects must be receiving MTX (oral or parenteral) at a dose of at least 10 mg/week for =6 months and at a stable dose and route of administration for =8 weeks prior to randomization (Day 0); 4. Subjects must receive at least 5 mg of folic acid or folinic acid per week at a stable dose for at least 4 weeks prior to randomization (Day 0); 5. Subjects must have at least 8 painful/tender and 6 swollen joints (based upon 68/66 joint counts) at screening and baseline (Day 0); 6. Subjects must have an elevated CRP level (defined as > the upper limit of normal [ULN] for the central lab) or an elevated ESR (defined as > the upper limit of normal [ULN] for the local lab) at screening; 7. Availability of normal chest X-ray within the last 6 months (i.e., no evidence of TB or chest infection). Patients who are clinically asymptomatic with minor changes consistent with rheumatoid lung are acceptable. # In Argentina, the chest X-ray must have been obtained within the last 1 month. 8. Subjects may be receiving: # Oral steroids at a stable dose of =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria 1. Use of intra-articular corticosteroid injections within one month prior to randomization (Day 0); 2. Use of other anti-arthritic treatments not mentioned in the above inclusion criteria, including approved or experimental oral, topical, or injectable biologics or drugs, or devices within 3 months or 5 half-lives (whichever is longer) prior to randomization (Day 0); 3. Pregnant or nursing females; 4. Subjects who have received prior treatment with tranilast; 5. Subjects who have any known hypersensitivity to any of the excipients contained in the study drug formulation; 6. Use of any of the following other medications: (a) oral hypoglycemic agents: tolbutamide, glipizide, glimepiride, glyburide, repaglinide, nateglinide, or a thiazolidenedione (“glitazones”, e.g. rosiglitazone); (b) warfarin or coumarol; (c) phenytoin, paclitaxel, fluconazole, amiodarone, or isoniazid; (d) a uricosuric agent for gout; or (e) an investigational medication or participation in an investigational study within 3 months of Day 0 7. Subjects with any laboratory test at screening considered significantly abnormal. The following will be considered significantly abnormal: # alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase =1.25-times the upper limit of normal (ULN) or # cytopenia (to include any of the following: WBC 5 mm induration. Additionally in Czech Republic, the TB skin test result must be assessed by a pneumonologist; 15. Has any other significant medical disease, mental impairment or other clinically significant abnormality on physical, neurological, laboratory, vital signs or ECG examination that the investigator or Sponsor believes would be detrimental to the subject or compromise the study; 16. Sub
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of tranilast at two different dosages compared to placebo in subjects with active RA when added to continuing MTX therapy.;Secondary Objective: To evaluate the safety and tolerability of tranilast at two different dosages compared to placebo in patients with RA recieving comcomitant MTX; To identify any significant differences in the safety or efficacy profile of the two doses of tranilastin patients with RA when added to continuing MTX therapy;Primary end point(s): Primary Endpoint: The primary efficacy analysis will utilize the Efficacy Population and compare the proportions (%) of subjects achieving an ACR20 response in the tranilast 300 mg/day group and the placebo group at Week 12. This analysis will utilize an LOCF approach and results will be utilized by the Sponsor to determine the efficacy potential for tranilast in RA. In addition, the primary endpoint will also be analyzed for the MITT population, but this will not be considered the primary efficacy analysis for this study. Non-responder imputation (all-cause dropouts and subjects with missing efficacy data at Week 12 are considered non-responders) will be utilized for this MITT population analysis These analyses will be performed using the Cochran-Mantel-Haenszel chi-square test with participation in the PK sub-study as a stratification factors. However, if any of the resultant cells for prior exposure to biologic treatments has <2 placebo patients, the Cochran-Mantel-Haenszel chi-square test will adjust only for geographic region. The null hypothesis of equality of ACR20 response rates will be assessed using a two-sided test at the 5% level of significance. | — |
Countries
Bulgaria, Czech Republic, Germany, Poland, United Kingdom
Outcome results
None listed