Resumen

El propósito de este estudio es evaluar si BMS-817399 en combinación con metotrexato es eficaz en el tratamiento de la artritis reumatoide moderada a grave.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Male or female subjects, 18 years of age or older, with rheumatoid arthritis (RA) for at least 6 months prior to screening
Subjects must have a tender joint count of at least 6 (28 joint count), swollen joint count of at least 6 (28 joint count) at screening. All subjects must have clinical evidence of synovitis in one hand/wrist at screening
Serum C-reactive protein (hsCRP) above upper limits of normal at screening
Subjects must have been treated with and tolerated Methotrexate (MTX) therapy at a weekly oral or parenteral dose ≥ 10 mg for ≥ 4 months prior to screening. Dose must be stable, with no change in route of administration, for ≥ 6 weeks prior to randomization. A MTX weekly dose as low as 7.5 mg is permitted if intolerance to doses ≥10 mg has been documented in the subject's medical history
Subjects must be receiving folic acid, folinic acid, or leucovorin supplementation at a stable dose for at least 4 weeks prior to randomization
Subjects who were previously treated with up to two tumor necrosis factor α (TNF-α) inhibitors
If taking antimalarials (e.g. hydroxychloroquine or chloroquine), subject must have been on a stable dose for ≥ 4 months prior to randomization
If taking non-steroidal anti-inflammatory drugs (NSAIDs), subjects must have been on stable doses for ≥ 2 weeks prior to randomization
If taking oral corticosteroids, daily doses must be ≤ 10 mg/day of prednisone or equivalent and stable for ≥ 4 weeks before randomization
Subject is willing to participate to the study and has signed the informed consent prior to undergoing any screening procedures
Women of childbearing potential (WOCBP) and men must agree to use at least two acceptable methods to avoid pregnancy for the entire study period and until 60 days (for women) and 90 days (for men) after the last dose of BMS-817399. WOCBP must have a negative urine pregnancy test at screening, randomization and at scheduled visits throughout the study

Criterios de exclusión

Arthritis onset prior to 16 years of age or subjects with documented juvenile RA
Subjects who are bed- or wheelchair-bound
Subjects with other autoimmune diseases or arthritis syndromes
Women who are pregnant, breastfeeding or with a positive pregnancy test at screening or prior to randomization
Subjects who have any condition that could impact upon the absorption of study drug (i.e., gastric stapling, duodenal surgery, malabsorption syndrome)
Subjects with a history of, or a concurrent severe, progressive, or uncontrolled disease (other than RA) that in the opinion of the investigator might place the subject at unacceptable risk for participation in this study
Subjects who have present or previous (last 5 years) malignancies, except history of cured squamous or basal skin cell carcinoma or cured breast or cervical cancer
Subjects at risk for tuberculosis (TB) or with evidence of TB clinical history, chest X rays or tuberculin skin test
Subjects with evidence of active or latent bacterial or viral infections (including human immunodeficiency virus); Positive blood screen for hepatitis B surface antigen or hepatitis C antibody
Subjects with any serious bacterial infection within the last 2 months, unless treated and resolved with antibiotics
Subjects who have clinically significant drug or alcohol abuse or known cirrhosis including alcoholic cirrhosis
If a subject has received any of the following treatments, the indicated washout period prior to randomization must be followed:
Oral or injectable azathioprine, gold, D-Penicillamine, cyclosporine, anakinra, etanercept, parenteral or intra-articular corticosteroids: 30 days
Leflunomide: 6 months unless an active washout with Cholestyramine has been performed
Mycophenolate mofetil, cyclophosphamide, tacrolimus or other immunosuppressant: 3 months
Adalimumab, Infliximab, Golimumab, Certolizumab pegol, Abatacept or Tocilizumab: 60 days
Rituximab or any B-cell depleting agent: 1 year
Use CYP3A4 inhibitors or inducers during the study
Subjects with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5x upper limit of normal (ULN), total bilirubin ≥ 1.4x ULN, estimated glomerular filtration rate (GFR) \< 50 mL/min/1.73m2, hemoglobin \< 10.0 g/dL, white blood cell count \< 3,500/mm3, absolute neutrophil count \< 1,700/mm3 or platelets \< 125,000/mm3

Intervenciones

drug

Placebo

Tablets, Oral, 0 mg, twice daily, 12 weeks

drug

BMS-817399

Tablets, Oral, 200 mg, twice daily, 12 weeks

drug

BMS-817399

Tablets, Oral, 400mg, twice daily, 12 weeks

Ubicaciones

Local Institution

Buenos Aires, Buenos Aires, Argentina

Local Institution

Buenos Aires, Buenos Aires, Argentina

Local Institution

Capital Federal, Buenos Aires, Argentina

Local Institution

San Miguel de Tucumán, Tucumán Province, Argentina

Patrocinadores

PrincipalBristol-Myers Squibb

Estudio multicéntrico, aleatorizado, doble ciego, controlado con placebo para evaluar la eficacia, seguridad, tolerabilidad y farmacocinética de BMS-817399 en adultos con artritis reumatoide activa, moderada a grave, y respuesta inadecuada a metotrexato

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Placebo

BMS-817399

BMS-817399

Ubicaciones

Local Institution

Local Institution

Local Institution

Local Institution

Patrocinadores