A Phase II, Randomized Multi-Center, Double-Blind Study of Tranilast with Concomitant Methotrexate (MTX) Compared to MTX Alone in Patients with Active Rheumatoid Arthritis (RA).
- Conditions
- Patients with active rheumatoid arthritis who are on a stable dose of methotrexate
- Registration Number
- EUCTR2008-006917-25-DE
- Lead Sponsor
- uon Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 250
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 <10 mg/day of prednisone (or equivalent
corticosteroid dose) if previously taken for at least one month prior to
randomization (Day 0);
# Chronic NSAIDs if taken at a stable dose for at least one month prior to
randomization (occasional use of NSAIDs for relief of headaches menstrual
cramps, and minor pain unrelated to RA is allowed);
# Hydroxychloroquine if taken at a stable dose of 200-400 mg PO daily or
chloroquine if taken at a stable dose of up to 250 mg PO daily for at least 3
months prior to randomization with no evidence of ocular toxicity as
documented by ophthalmologic exam within the previous 12 months;
# Sulfasalazine if taken at a stable daily dose of up to 3000 mg PO for at least 3
months prior to randomization;
9. Females of childbearing potential must agree to continue to use adequate
contraception (i.e., hormonal [oral, depot, patch], IUD, or barrier and spermicide)
throughout the study and for at least 1 month following their last study visit;
# Females of childbearing potential in Argentina must agree to monthly urine
pregnancy testing as well as the contraceptive measures described above
10. In the opinion of the investigator, the subject will be compliant and have a high
probability of completing the study and all required procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
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 <3.5x103/µL; Hgb <10 g/dL;
platelets <100x103/µL; neutrophils absolute <1.5x103/µL; lymphocytes
absolute <0.8x103/µL) or
# Creatinine =1.25-times the upper limit of normal (ULN)
8. Has an elevated total bilirubin (e.g., outside the upper limit of normal), which
persists upon repeat or a history of Gilbert’s syndrome;
9. History of clinically significant renal or hepatic dysfunction or disease;
10. Has a history of or has a current, clinically significant major psychiatric disorder
(e.g., major depressive disorder, psychosis, schizophrenia) according to the
criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition (DSM-IV-TR)
[Exception; subjects with depression that has been adequately controlled for at
least 6 months may enroll in the study];
11. Has a history of alcohol or drug dependence or abuse as defined by DSM-IV-TR
criteria within the last 2 years;
12. Has a history of uric acid urolithiasis or gout;
13. Has a clinically significant systemic infection (e.g., chronic or acute infection, UTI,
URI) within 30 days of Day 0, or a history or presence of recurrent or chronic
infection (e.g., viral infections, including hepatitis B or C, HIV), bacterial
infections, systemic fungal infections, or syphilis);
14. Has evidence of tuberculosis as indicated by subjects with a positive tuberculin
(TB) skin test at screening or within the 30 days prior to screening (defined as
=10 mm induration);
# For sites in Argentina and Czech Republic: A positive TB skin test will be
defined as >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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method