subjects with rheumatoid arthritis (RA) who are on background therapy with methotrexate (MTX) MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Code: BMS-582949
Pharmaceutical Form: Tablet
Current Sponsor code: BMS-582949
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of th
Sponsors
Bristol Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent a) Subjects must be able to provide informed, written consent. 2) Target Population a) Subjects must meet the criteria of the American Rheumatism Association (1987) for the diagnosis of RA (Arnett et al, 1988) (Appendix 3). The disease must have been diagnosed for = 6 months prior to screening. b) Subjects must have been taking MTX for at least 3 months at a weekly dose of 7.5 to 30 mg, inclusive, and at a stable dose for 28 days prior to treatment (Day 1). Use of parenteral MTX is acceptable as clinically indicated if subjects cannot tolerate or absorb oral MTX. c) Subjects must be MTX inadequate responders defined as currently having 6 or more swollen joints and 8 or more tender joints at the screening visit (refer to Inclusion number 5, disease activity) 3) Age and Sex a) Men and women at least 18 years of age. Men and women of childbearing potential are eligible if they are practicing effective contraceptive measures. Because subjects are taking background therapy such as methotrexate for treatment of RA, which has potential risks associated with its use in pregnancy, subjects will be re-advised on the use of reliable contraceptive methods and on the potential risks to a pregnancy. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. 4) Concomitant Medication (Anti-rheumatic Treatment) a) MTX alone: Subjects who are treated only with methotrexate will not require washout. b) MTX plus DMARDs other than sulfasalazine or anti-malarials (eg hydoxychloroquine, chloroquine): Subjects who are treated with MTX in combination with another anti-rheumatic treatment (DMARD) will require washout of the other DMARDs. c) Drug stabilization requirements i) If subjects are taking sulfasalazine and/or anti-malarials, which are allowed as concomitant therapy in this study, they must be on a stable dose for 25 out of 28 days prior to treatment (Day 1). ii) All DMARDs (except MTX, sulfasalazine and anti-malarials) must be discontinued at least 28 days prior to treatment (Day 1). In the case of leflunamide, the subject can be washed out with cholestyramine according to manufacturers recommendations. iii) Oral corticosteroid treatment must have been reduced to = 10 mg prednisone or equivalent per day for at least 14 days and stabilized for at least 11 out of 14 days prior treatment (Day 1). iv) Subjects who have had previous treatment with any biologic/immunosuppresant therapy for RA require wash-out for a period of at least 28 days or 5 half lives whichever is longer or a minimum of 3 months for any biologic agent with an unknown half life, prior to treatment (Day 1). v) Subjects requiring NSAIDs must be on a stable dose for at least 14 days prior to Day 1 dose. d) Prior treatment with up to two anti-TNFa inhibitors will be allowed. 5) Disease Activity a) For subjects receiving MTX alone or MTX plus sulfasalizine and/or antimalarials: At the screening visit, subjects must have the following disease activity: i) 6 or more swollen joints (66 joint count) and ii) 8 or more tender joints (68 joint count) and iii) C-reactive protein (CRP) > ULN or erythrocyte sedimentation rate (ESR) (Westergren Method) > 28 mm/hr (Both tests are required. Results will be used from the screening visit to qualify for the study.) b) For subje
Exclusion criteria
Exclusion criteria: 1) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the last dose of investigational product. b) Women who are pregnant or breastfeeding c) Women with a positive pregnancy test on enrollment or prior to investigational product administration. d) Men who are unwilling or unable to use an acceptable method of birth control for the entire study period. 2) Medical History and Concurrent Diseases a) Any clinically significant acute or chronic illness other than RA that is severe, progressive or uncontrolled at the time of screening. This includes any current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, musculoskeletal, genitourinary, or thyroid disease. b) Any major surgery within 4 weeks of screening or planned/scheduled surgery requiring hospitalization during the time of the study. c) Blood transfusion within 4 weeks of screening. d) Donation of blood or plasma to a blood bank or in a clinical study within 4 weeks of screening. e) Any condition that could impact upon the absorption of study drug. (ie, gastric ulcer requiring therapy, gastric stapling, duodenal surgery, malabsorption syndrome). f) Subjects (currently or within 3 months) requiring chronic or intermittent medical therapy or surgical intervention for gastrointestinal disease including gastrointestinal ulceration, chronic heartburn, esophageal reflux, gastric or duodenal ulcer and/or gastritis. g) Any infection requiring systemic anti-microbial treatment that completed within 4 weeks of enrollment. h) Major infection requiring hospitalization or receipt of intravenous antibiotics within 2 months prior to enrollment. i) Subjects at risk for tuberculosis (TB). j) Have a history of opportunistic infection and/or evidence of active infection including but not limited to HIV, Hepatitis B or C viruses. k) History of lymphoproliferative disease, including lymphoma, or signs suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size, location, or clinically significant splenomegaly. l) Any known malignancy or history of malignancy within 5 years including carcinoma in situ prior to enrollment, with the exception of basal cell or squamous cell carcinoma of the skin that has been excised with no evidence of recurrence (squamous cell carcinoma of other location is exclusionary). m) Subjects who have received treatment with any investigational drug within the previous 30 days or 5 half-lives of the Day 1 dose, whichever is greater. n) Subjects who have received a live vaccine within 3 months of Day 1 dosing. 3) Physical and Laboratory Test Findings a) Subjects at screening with PT and/or aPTT and/or INR values = 1.05 X ULN. b) Subjects at screening with ALT or AST elevations = 1.5 X ULN or with a history of frequent or recent ALT or AST elevations are excluded. c) Subjects at screening with CK elevations = 2 X ULN or with a history of frequent or recent CK elevations are excluded. d) Any clinically significant (as determined by the investigator) vital signs and/or physical examination finding. e) Positive blood screen for hepatitis B surface Ag and hepatitis C antibody. f) Chest radiograph at screening showing evidence of chronic infection, malignancy or inflammation. g) Screening ECG showing clinically significant abnormalities. 4) Proh
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the clinical efficacy of BMS-582949 at a dose of 300 mg once a day (qd) compared to placebo at 12 weeks as measured by ACR 20 in subjects with RA who are on background therapy with MTX.;Secondary Objective: • To assess the safety and tolerability of BMS-582949 in subjects with RA • To assess the proportion of subjects who achieve an ACR 50 or ACR 70 response in each treatment group • To assess the reduction in disease activity over time as measured by the DAS28 and ACR-N over 16 weeks • To assess the proportion of subjects achieving a 20 percent change in the assessment of pain, disease activity and fatigue using the American College of Rheumatology (ACR) Disease Activity Visual Assessment Scales (VAS) • To assess the percent change in physical function as measured by the disability index of the Health Assessment Questionnaire (HAQ) over 16 weeks of treatment in each treatment group. • To determine the trough plasma concentrations of BMS-582949 (Cmin).;Primary end point(s): The primary study endpoint will be the percent of subjects who achieve an ACR 20 response following 12 weeks of treatment and to determine the difference in ACR 20 response between BMS-582949 compared to placebo following 12 weeks of treatment. | — |
Countries
Czech Republic, France, Spain
Outcome results
None listed