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

This study has been completed.
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT00760864
First received: September 24, 2008
Last updated: June 9, 2010
Last verified: June 2010
  Purpose

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.


Condition Intervention Phase
Arthritis, Rheumatoid
Drug: TAK-715 and methotrexate
Drug: Methotrexate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety and Efficacy of Oral TAK-715 in the Treatment of the Signs and Symptoms of Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Composite ACR 20% improvement response rate from baseline with 3 of the following: pain assessment; disease activity; physical function; C-reactive protein and erythrocyte sedimentation rate. [ Time Frame: Week 6 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Composite ACR 50% improvement response rate from baseline with 3 of the following: swollen-tender joint counts; pain assessment; disease activity; physical function; C-reactive protein and erythrocyte sedimentation rate. [ Time Frame: Week 6. ] [ Designated as safety issue: No ]
  • Composite ACR 70% improvement response rate from baseline with 3 of the following: swollen-tender joint counts; pain assessment; disease activity; physical function; C-reactive protein and erythrocyte sedimentation rate. [ Time Frame: Week 6. ] [ Designated as safety issue: No ]
  • Change from baseline in swollen and tender joint counts. [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Change from baseline in patient's assessment of pain. [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Change from baseline in patient's global assessment of disease activity. [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Change from baseline in physician's assessment of disease activity. [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Change from baseline in patient's self assessment of physical function using the Health Assessment Questionnaire. [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Change from baseline in C-reactive protein. [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Change from baseline in erythrocyte sedimentation rate. [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Time to American College of Rheumatology 20% improvement response. [ Time Frame: Weeks 2, 4, and 6 ] [ Designated as safety issue: No ]
  • Time to American College of Rheumatology 50% improvement response. [ Time Frame: Weeks 2, 4, and 6 ] [ Designated as safety issue: No ]
  • Time to American College of Rheumatology 70% improvement response. [ Time Frame: Weeks 2, 4, and 6 ] [ Designated as safety issue: No ]

Enrollment: 432
Study Start Date: August 2004
Study Completion Date: September 2005
Primary Completion Date: September 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TAK-715 25 mg BID Drug: TAK-715 and methotrexate
TAK-715 25 mg, tablets, orally, twice daily and methotrexate stable dose for up to 6 weeks.
Experimental: TAK-715 50 mg BID Drug: TAK-715 and methotrexate
TAK-715 50 mg, tablets, orally, twice daily and methotrexate stable dose for up to 6 weeks.
Experimental: TAK-715 100 mg BID Drug: TAK-715 and methotrexate
TAK-715 100 mg, tablets, orally, twice daily and methotrexate stable dose for up to 6 weeks.
Active Comparator: Methotrexate Drug: Methotrexate
TAK-715 placebo-matching, tablets, orally, twice daily and methotrexate stable dose for up to 6 weeks

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00760864

Sponsors and Collaborators
Takeda
Investigators
Study Director: VP Biological Sciences Takeda
  More Information

No publications provided

Responsible Party: Sr. VP, Clinical Science, Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier: NCT00760864     History of Changes
Other Study ID Numbers: 01-03-TL-715-005, 2004-002157-30, U1111-1114-2984
Study First Received: September 24, 2008
Last Updated: June 9, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Rheumatoid Arthritis
Drug Therapy

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014