Safety and Efficacy of TAK-715 in Subjects With Rheumatoid Arthritis

• Status: Completed
• Trial end date: 2005-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the safety and efficacy of TAK-715, twice daily (BID), in the treatment of rheumatoid arthritis signs and symptoms in patients with a partial response to methotrexate.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Takeda
• Treatments: Methotrexate

Criteria

Inclusion Criteria:

• Had a diagnosis of rheumatoid arthritis using American College of Rheumatology criteria of at least 6 months duration.

• A female subject of childbearing potential who is sexually active must agree to use adequate contraception, and must be neither pregnant nor lactating from Screening throughout the duration of the study.

• Had a physical examination at Screening that revealed no clinically significant abnormalities (other than rheumatoid arthritis) in the investigator's opinion.

• Had clinical laboratory test results at Screening that were normal or, if abnormal, were not clinically significant in the investigator's opinion.

• Had a 12-lead electrocardiogram at Screening that was normal or, if abnormal, was not clinically significant in the investigator's opinion.

• Had a chest x-ray within 6 months prior to or during the Pretreatment Period that, in the investigator's opinion, showed no signs of active tuberculosis and was free of clinically significant findings.

• Had a negative purified protein derivative skin test for tuberculosis (less than or equal to 5 mm in duration) during the Screening Period.

• Had been receiving oral or parenteral methotrexate for at least 6 months prior to Baseline and must have been on a stable dose (12.5 to 25 mg per week, inclusive) of methotrexate for at least 4 weeks prior to Baseline. The subject must have been on a dose of folic acid at greater than or equal to 1 mg/day.

• Had at least 6 swollen and 9 tender joints using the 66/68 joint count scale at Screening and Baseline.

• At Screening, the subject must have had a C-reactive protein of at least 1.2 mg/dL or an erythrocyte sedimentation rate of at least 28 mm/hr.

• For individuals who were taking a systemic corticosteroid, the maintenance dose of prednisone, or its equivalent, could not exceed 10 mg/day and must have been stable for at least 4 weeks prior to Baseline and must have remained at that stable dose throughout the study.

• For individuals who were taking a nonsteroidal anti-inflammatory drug for the treatment of rheumatoid arthritis, the maintenance dose of the nonsteroidal anti-inflammatory drug must have been stable for at least 4 weeks prior to Baseline and must have remained at that stable dose throughout the study.

Exclusion Criteria:

• Had been diagnosed with any type of arthritis at age 16 or younger.

• Had a history of a clinically significant illness, medical condition, or laboratory abnormality within 3 months prior to Baseline that, in the investigator's opinion, would preclude the subject's participation in the study.

• Had a known history of human immunodeficiency virus infection.

• Had a known history of hepatitis B or C.

• Had uncontrolled hypertension.

• Had moderate or severe liver disease at Screening, as defined by at least 1 of the following conditions:

• Aspartate transaminase or alanine transaminase greater than 1.2 times the upper limit of normal.

• Total bilirubin greater than 1.2 times upper limit of normal (excluding subjects diagnosed with Gilbert's disease).

• Alkaline phosphatase greater than 1.5 times upper limit of normal.

• Had elevated serum creatinine level for age and gender at Screening.

• Had hemoglobin less than 9.0 g/dL, white blood cell count of less than 3000/mm3, or a platelet count less than 100,000/mm3 at Screening.

• Had an American College of Rheumatology revised rheumatoid arthritis functional status of IV at Screening.

• Had taken, is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

• A disease-modifying antirheumatic drug or a biologic agent other than methotrexate in the 8 weeks prior to Baseline, including:

• Plaquenil.

• Sulfasalazine.

• Tetracycline.

• infliximab (Remicade®).

• leflunomide (Arava®).

• etanercept (Enbrel®).

• anakinra (Kineret®).

• Had failed therapy due to lack of efficacy with any anti- tumor necrosis factor agent.

• Had failed due to lack of efficacy with more than 2 disease-modifying antirheumatic drugs (other than methotrexate).

• Had received any intra-articular, intramuscular, or intravenous corticosteroids within 4 weeks prior to Baseline.

• The subject had any previous use of cyclophosphamide, chlorambucil, or other alkylating agent.

• Was at high risk of an opportunistic infection because of a compromised immune system, in the investigator's opinion, with the exception of subjects receiving chronic steroid treatment.

• Had a history of or a current inflammatory condition with signs and symptoms that could have confounded the diagnosis of rheumatoid arthritis (eg, connective tissue disease, systemic lupus erythematosus, psoriasis, psoriatic arthritis, spondyloarthropathy).

• Had been diagnosed as having a secondary, non-inflammatory type of arthritis (eg, osteoarthritis or fibromyalgia) that, in the investigator's opinion, was symptomatic enough to interfere with the evaluation of the efficacy of the study drug on the subject's primary diagnosis of rheumatoid arthritis.

• Had a history of drug abuse or alcohol abuse within the past 2 years.

• The subject had a body mass index greater than 35 at Screening.

• Had a history of cancer, other than basal cell carcinoma, that had not been in remission for at least 5 years prior to the first dose of study drug.

• Had a known hypersensitivity to TAK-715 or its constituents.