Effect of Febuxostat on Joint Damage in Hyperuricemic Subjects With Early Gout

NCT01078389 | Completed Phase 2 Results DMC

• 2 other identifiers: TMX-67_204U1111-1113-8098
• Study Type: interventional
• Target: 314
• Locations: 1 country
• Sites: 56

Brief Summary

This purpose of this study is to assess the effect of febuxostat, once daily (QD), on joint damage in patients with elevated serum urate levels and gout.

Conditions

Joint Damage

Keywords

Gout; Hyperuricemia; Uric Acid; Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Score of the Single Affected Joint

  The single affected joint was defined as the joint with the history of the first acute gout flare. Radiographs (X-rays) of this single joint in the hands or feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst). Individual erosion scores were summed to a maximum erosion score of 5 for joints in the hands and 10 for joints in the feet. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement.

  Baseline and Month 24

Secondary Outcomes (4)

• Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Scores From Full Hands and Feet Radiographs

  Baseline and Month 24

• Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Scores From Full Hands and Feet Radiographs

  Baseline and Month 24

• Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint

  Baseline and Month 24

• Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Score of the Single Affected Joint

  Baseline and Month 24

Study Arms (2)

Febuxostat 40 mg or 80 mg

EXPERIMENTAL

Febuxostat 40 mg or 80 mg (based on serum urate levels at Day 14), capsules, orally, once daily for up to 24 Months.

Drug: Febuxostat

Placebo

PLACEBO COMPARATOR

Febuxostat placebo-matching capsules, orally, once daily for up to 24 Months.

Drug: Placebo for Febuxostat

Interventions

Febuxostat DRUG

Febuxostat capsules

Also known as: Uloric, TMX-67

Febuxostat 40 mg or 80 mg

Placebo for Febuxostat DRUG

Febuxostat placebo-matching capsules

Placebo

Eligibility Criteria

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

You may qualify if:

• The participant, or the participant's legally acceptable representative, signs a written informed consent form/Health Insurance Portability \& Accountability Act (HIPAA) Authorization prior to the initiation of any study procedures.
• Must have a history or presence of gout defined as having one or more of the following conditions of the American Rheumatism Association (ARA) preliminary criteria for the diagnosis of gout
• A tophus proven to contain urate crystals by chemical or polarized light microscopic means and/or
• Characteristic urate crystals in the joint fluid and/or
• History of at least 6 of the following clinical, laboratory and x-ray phenomena\*: \*More than one flare criteria will be excluded for the purpose of this study if the participant has a history of only a single acute gout flare.
• More than one attack of acute arthritis\*
• maximum inflammation developed within 1 day
• monoarticular arthritis
• redness observed over joints
• first metatarsophalangeal joint painful or swollen
• unilateral first metatarsophalangeal joint attack
• unilateral tarsal joint attack
• tophus (proven or suspected)
• hyperuricemia
• asymmetric swelling within a joint on x-ray

You may not qualify if:

• Previously on urate-lowering therapy (allopurinol, febuxostat or probenecid).
• Has secondary hyperuricemia (eg due to myeloproliferative disorder or organ transplant).
• Has a history of xanthinuria.
• Has a known hypersensitivity to any component of the febuxostat formulation.
• Has rheumatoid arthritis.
• Has active peptic ulcer disease.
• Has a history of cancer, except basal cell carcinoma of the skin, which has not been in remission for at least 5 years prior to the first dose of study medication.
• Has experienced either a myocardial infarction (MI) or stroke within 90 days prior to the Screening visit.
• Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) values greater than 2.0 the upper limit of normal during the Screening period.
• Has a significant medical condition and/or conditions that would interfere with the treatment, safety or compliance with the protocol at the discretion of the Investigator.
• Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse with 5 years prior to the Screening visit. Participant consumes \>14 alcoholic beverages/week.
• Has received any investigational medicinal product within 30 days prior to the Screening visit. In addition, the participant has been previously randomized into this study and received at least one dose of double blind study drug treatment.
• Has an estimated Glomerular filtration rate (eGFR) \<60 mL/min calculated using the Modification of Diet in Renal Disease (MDRD) formula by the Central Laboratory.
• Has a serum creatinine at Screening greater than 2.0 mg/dL.
• Has a known history of infection with hepatitis B, hepatitis C or human immunodeficiency virus.

Sponsors & Collaborators

• Takeda: lead

Study Sites (56)

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Mesa, Arizona, United States

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Tucson, Arizona, United States

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Burbank, California, United States

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Carmichael, California, United States

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Costa Mesa, California, United States

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Irvine, California, United States

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Orange, California, United States

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Rancho Cucamonga, California, United States

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San Diego, California, United States

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San Luis Obispo, California, United States

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Trumbull, Connecticut, United States

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Boynton Beach, Florida, United States

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Daytona Beach, Florida, United States

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Fort Lauderdale, Florida, United States

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Hialeah, Florida, United States

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Miami, Florida, United States

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Sanford, Florida, United States

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Tampa, Florida, United States

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Winter Park, Florida, United States

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Honolulu, Hawaii, United States

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Arlington Heights, Illinois, United States

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Avon, Indiana, United States

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Greenfield, Indiana, United States

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Wichita, Kansas, United States

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Rockport, Maine, United States

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Chaska, Minnesota, United States

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Belzoni, Mississippi, United States

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Olive Branch, Mississippi, United States

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Billings, Montana, United States

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Missoula, Montana, United States

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Bellevue, Nebraska, United States

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Henderson, Nevada, United States

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Las Vegas, Nevada, United States

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Albuquerque, New Mexico, United States

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Charlotte, North Carolina, United States

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Lenoir, North Carolina, United States

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Shelby, North Carolina, United States

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Dayton, Ohio, United States

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Franklin, Ohio, United States

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Willoughby Hills, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Eugene, Oregon, United States

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Duncansville, Pennsylvania, United States

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East Providence, Rhode Island, United States

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Columbia, South Carolina, United States

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Rapid City, South Dakota, United States

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Kingsport, Tennessee, United States

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Austin, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Southlake, Texas, United States

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Sugar Land, Texas, United States

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Arlington, Virginia, United States

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Burke, Virginia, United States

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Manassas, Virginia, United States

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Kenosha, Wisconsin, United States

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Related Publications (1)

• Dalbeth N, Saag KG, Palmer WE, Choi HK, Hunt B, MacDonald PA, Thienel U, Gunawardhana L. Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study. Arthritis Rheumatol. 2017 Dec;69(12):2386-2395. doi: 10.1002/art.40233.

  PMID: 28975718 DERIVED

Related Links

• Uloric Package Insert

MeSH Terms

Conditions

Gout; Hyperuricemia

Interventions

Febuxostat

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Director, Clinical Science
• Organization: Takeda

clinicaltrialregistry@tpna.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2010
• First Posted: March 2, 2010
• Study Start: March 1, 2010
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: September 10, 2014
• Results First Posted: September 10, 2014

Record last verified: 2014-09

Locations

US (56)