Efficacy and Safety of TAK-783 in Subjects With Rheumatoid Arthritis

NCT00760968 | Completed Phase 2

• 3 other identifiers: TAK-783-EC2012006-003054-26U1111-1114-0266
• Study Type: interventional
• Target: 224
• Locations: 6 countries
• Sites: 25

Brief Summary

The purpose of this study is to determine the efficacy and safety of TAK-783, once daily (QD), taken in combination with methotrexate in subjects with rheumatoid arthritis.

Conditions

Arthritis, Rheumatoid

Keywords

Rheumatoid Arthritis; Drug Therapy

Outcome Measures

Primary Outcomes (8)

• Percent of subjects with greater than or equal to 20% improvement in Arthritis Signs and Symptoms according to the American College of Rheumatology

  Weeks 2, 4, 8, and 12 or Final Visit.

• Change from Baseline in Treatment-emergent adverse events.

  Weeks 2, 4, 8, and 12 or Final Visit.

• Change from Baseline in Vital signs.

  Weeks 2, 4, 8, and 12 or Final Visit.

• Change from Baseline in Electrocardiogram findings.

  Weeks 2, 4, 8, and 12 or Final Visit.

• Change from Baseline in Spirometry tests.

  Weeks 2, 4, 8, and 12 or Final Visit.

• Change from Baseline in Hematology Laboratory tests.

  Weeks 2, 4, 8, and 12 or Final Visit.

• Change from Baseline in Chemistry Laboratory tests.

  Weeks 2, 4, 8, and 12 or Final Visit.

• Change from Baseline in Urinalysis Laboratory tests.

  Weeks 2, 4, 8, and 12 or Final Visit.

Secondary Outcomes (13)

• Percent of subjects with greater than or equal to 50% improvement in Arthritis Signs and Symptoms according to the American College of Rheumatology

  Weeks 2, 4, 8, and 12 or Final Visit.

• Percent of subjects with greater than or equal to 70% improvement in Arthritis Signs and Symptoms according to the American College of Rheumatology

  Weeks 2, 4, 8, and 12 or Final Visit.

• Change from Baseline in individual Arthritis Signs and Symptoms according to the American College of Rheumatology.

  Weeks 2, 4, 8, and 12 or Final Visit.

• Percent change from Baseline in the disability index of the Heath Assessment Questionnaire, based on the American College of Rheumatology criteria.

  Weeks 2, 4, 8, and 12 or Final Visit.

• Percent Change from Baseline in 36-Item Short-Form Quality of Life Assessments

  Weeks 4 and 12 or Final Visit.

Study Arms (2)

TAK-783 100 mg QD + Methotrexate

EXPERIMENTAL

Drug: TAK-783 and methotrexate

Methotrexate

ACTIVE COMPARATOR

Drug: Methotrexate

Interventions

TAK-783 and methotrexate DRUG

TAK-783 100 mg, tablets, orally, once daily and methotrexate stable dose therapy for up to 12 weeks.

Also known as: Rheumatrex®.

TAK-783 100 mg QD + Methotrexate

Methotrexate DRUG

TAK-783 placebo-matching tablets, orally, once daily and methotrexate stable dose therapy for up to 12 weeks.

Also known as: Rheumatrex®.

Methotrexate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Had a diagnosis of rheumatoid arthritis using American College of Rheumatology criteria of at least 6 months duration and less than or equal to 3 years.
• 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 and throughout the duration of the study.
• Had a physical examination that, in the investigator's opinion, reveals no clinically significant abnormalities (other than rheumatoid arthritis), at the Screening Visit.
• Had clinical laboratory test results that are normal or, if abnormal, are not clinically significant in the investigator's opinion, at the Screening and Baseline Visits.
• Had a 12-lead electrocardiogram that is normal during the Screening Period, or, if abnormal, is not clinically significant in the opinion of the investigator.
• Had a chest x-ray within 3 months prior to or during the Pretreatment Period that, in the opinion of the investigator, is free of clinically significant findings.
• Had a negative purified protein derivative skin test for tuberculosis (less than or equal to 5 mm in duration) at screening and a negative tuberculosis screening history.
• Was receiving oral or parenteral methotrexate for at least 6 months prior to the Baseline Visit, and must be on a stable dose of methotrexate for at least 8 weeks prior to the Baseline Visit.
• At the Screening and Baseline Visits, the subject must have at least 6 swollen and 9 tender/painful joints using the 66/68 joint count scale.
• At the Screening Visit, the subject must have a C - reactive protein of at least 1.2 mg/dL or an erythrocyte sedimentation rate of at least 28 mm/hr.
• If taking a systemic corticosteroid, the maintenance dose of prednisone, or its equivalent, must be stable for at least 4 weeks prior to the Baseline Visit, may not exceed 10 mg/day and the subject should continue on that stable dose throughout the study.
• If taking a non-steroidal anti-inflammatory drug for the treatment of rheumatoid arthritis, the maintenance dose of the non-steroidal anti-inflammatory drug must be stable for at least 4 weeks prior to the Baseline Visit, and should continue on that stable dose throughout the trial.
• Had a forced expiratory volume in one second and a forced vital capacity greater than 80% of predicted at screening.

You may not qualify if:

• Had been diagnosed with any type of arthritis at age 16 or younger.
• Had achieved greater than or equal to 20% response improvement in rheumatoid arthritis signs and symptoms according to the American College of Rheumatology criteria during the placebo lead-in period.
• Had a history of a clinically significant illness, medical condition, or laboratory abnormality within 3 months prior to the Baseline Period 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, as defined by one or more of the following at the Screening Visit:
• Aspartate or alanine transaminase greater than 1.2 times the upper limit of normal.
• Total bilirubin greater than 1.2 times the upper limit of normal (excluding subject's diagnosed with Gilbert's Disease).
• Alkaline phosphatase greater than 1.5 times the upper limit of normal.
• Had elevated serum creatinine level for age and gender at the Screening Visit.
• Had hemoglobin less than 9.0 mg/dL, white blood cell count of less than 3000/mm3 or a platelet count less than 100,000/mm3 at the Screening Visit.
• Had an American College of Rheumatology revised rheumatoid arthritis functional status of IV at the Screening Visit.
• Was 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 TAK-783, including:
• Disease-modifying antirheumatic drugs or biologic agents other than methotrexate in the 12 weeks prior to the Baseline Visit, including:

Sponsors & Collaborators

• Takeda: lead

Study Sites (25)

Unknown Facility

Brno-Bohunice, Czechia

Location

Unknown Facility

Hlučín, Czechia

Location

Unknown Facility

Pilsen, Czechia

Location

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Prague, Czechia

Location

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Uherské Hradiště, Czechia

Location

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Zlín, Czechia

Location

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Daugavpils, Latvia

Location

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Riga, Latvia

Location

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Bucharest, Romania

Location

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Timișoara, Romania

Location

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Kemerovo, Russia

Location

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Moscow, Russia

Location

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Novosibirsk, Russia

Location

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Petrozavodsk, Russia

Location

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Saint Petersburg, Russia

Location

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Yaroslavl, Russia

Location

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Yekaterinburg, Russia

Location

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Košice, Slovakia

Location

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Martin, Slovakia

Location

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Nové Zámky, Slovakia

Location

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Piešťany, Slovakia

Location

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Poprad, Slovakia

Location

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Trnava, Slovakia

Location

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Donetsk, Ukraine

Location

Unknown Facility

Kyiv, Ukraine

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 24, 2008
• First Posted: September 26, 2008
• Study Start: August 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: June 11, 2010

Record last verified: 2010-06

Locations

LA (2); RO (2); CZ (6); SL (6); UA (2); RU (7)