Clinical trial NCT00326339 (phase 2, status: completed)
Conditions: rheumatoid arthritis
ICD codes: M06.9, M05.9, M06.08, M06.00, M06.011, M06.012, M06.019
Drugs: r788, placebo
SMILES: COC1=CC(NC2=NC=C(F)C(NC3=CC=C4OC(C)(C)C(=O)NC4=N3)=N2)=CC(OC)=C1OC, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          1. Patients must give written informed consent by signing an IRB-approved Informed
             Consent Form (ICF) prior to admission to this study.

          2. Males and females, 18 to 75 years of age, with active RA for at least 12 months
             (functional class I-III, e.g., not bed or wheelchair-bound) who have been receiving
             weekly doses of methotrexate (10-25 mg/week) for a minimum of 180 days, and who have
             been receiving a stable MTX dose of at least 15 mg without any change in route or
             change in folic acid supplementation for at least 30 days.

             Active RA is defined as the presence of (a)6 swollen joints (28 joint count); AND (b)6
             tender joints (28 joint count); AND (c) CRP level > ULN for the central reference
             laboratory.

             Patient may receive up to 10 mg per day of oral prednisone or steroid equivalent,
             NSAID therapy, hydroxychloroquine, chloroquine, minocycline, sulfasalazine, and
             doxycycline. The dose(s) must have been stable for at least 30 days and must not be
             changed during the washout, screening and treatment periods, unless dictated by
             tolerability requirements.

          3. Females of childbearing potential must be fully informed of the potential for
             methotrexate and R788 to adversely affect the fetus and must agree to use adequate (2
             methods) contraception during the study. These patients must not be lactating and must
             have a negative urine pregnancy test at the time of randomization and at each
             laboratory determination.

          4. The patient is in otherwise good health as determined by the Investigator on the basis
             of medical history, physical examination, and laboratory screening tests during the
             screening period, including the absence of clinically significant findings, such as
             HIV, HBV or HCV, interstitial pneumonitis or active pulmonary infection, on chest
             X-ray taken within 6 months prior to screening and a negative TB skin test, or
             abnormal liver function defined as known ALT >1.2xULN within the past 90 days.

          5. In the investigator's opinion, the patient has the ability to understand the nature of
             the study and any hazards of participation, and to communicate satisfactorily with the
             investigator and to participate in, and to comply with, the requirements of the entire
             protocol.

        Exclusion Criteria:

          1. The patient has a history of, or a concurrent, clinically significant illness, medical
             condition (other than arthritis) or laboratory abnormality that, in the Investigator's
             opinion, could affect the conduct of the study (these will be included in an exclusion
             log).

          2. The patient has a history of substance abuse, drug addiction or alcoholism.

          3. The patient is unable to abstain from alcohol during the study.

          4. The patient has a recent (past 5 years) history of, or treatment for, a malignancy
             other than basal skin cancer.

          5. The patient has received any investigational medication within 30 days prior to
             admission to the study.

          6. Any patient who has received any of the following treatments must abide by the
             indicated washout period:

               1. oral or injectable gold, azathioprine, penicillamine, anakinra require a 30 day
                  washout period prior to Day 1 dosing

               2. cyclosporine, abatacept, etanercept, infliximab or adalimumab require a 60 day
                  washout period prior to Day 1 dosing

               3. leflunomide requires a 60 day washout period prior to screening, unless the
                  patient has undergone cholestyramine washout at least 30 days prior to Day 1
                  dosing

               4. cyclophosphamide requires a 180 day washout period prior to Day 1 dosing

               5. Rituxan requires a 180 day washout period and normal CD19 count prior to Day 1
                  dosing

               6. parenteral or intra-articular corticosteroids require a 30 day washout period
                  prior to Day 1 dosing

          7. Patients with the following laboratory abnormalities: ALT > 1.2X ULN, creatinine >
             ULN, a neutrophil count < 2,500/mm3 or lymphocyte count < 800/mm3, Hgb < 10 g/dL,
             platelet count < 125,000/mm3 are excluded.

          8. Patients should not use CYP3A4 inhibitors from within 3 days of randomization until
             the end of study. R406 is metabolized by CYP3A4, and ketoconazole increases the R406
             AUC of a dose of R788 by approximately 2 fold.

          9. Patients should not use CYP3A4 inducers from within 3 days of randomization until the
             end of the study. Although glucocorticoids are inducers, a stable dose of no more than
             10 mg/day is allowed.