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

NCT ID: NCT01078389

Last Updated: 2014-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 314 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2013-09-30

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.

Detailed Description

Gout is caused by high levels of uric acid in the body, and is associated with a broad range of comorbidities including heart disease, chronic kidney disease and additional risk factors like obesity and high blood pressure. Hyperuricemia, which is defined as an elevation in serum urate levels, develops into gout when urate crystals form from supersaturated body fluids and settle in joints and other organs. Urate-lowering therapy is used to treat hyperuricemia in patients with gout.

Current treatments focus on initiating urate-lowering therapy in hyperuricemic gout patients who have experienced multiple acute gout flares within the past year. However, joint damage caused by crystal deposition may occur much earlier than previously considered. Monosodium urate crystals have been found present in the joints of people with hyperuricemia who do not have any symptoms. The presence of monosodium urate crystals would indicate that after the crystals form, they stay within the joint if serum urate levels are not reduced. Lowering uric acid levels and maintaining them may reduce acute gout flare episodes and possibly halt or reduce joint damage in patients with gout.

This study will evaluate the effect of febuxostat on joint damage in hyperuricemic patients with early gout. All patients will receive gout flare prophylaxis for the first 6 months of the study. Gout flares may also be treated throughout the study.

A variety of imaging techniques are in use to evaluate gout. Plain radiographs (x-rays), Magnetic Resonance Imaging (MRI) and Dual Energy Computed Tomography (DECT) will be utilized in this study. The modified Sharp/Van Der Heijde scoring method (named after Drs. Sharp and Van Der Heijde) for assessment of x-rays has been validated in patients with chronic gout and will be used in this study for evaluating erosion and joint space narrowing. Participants are expected to have 15 visits which will include plain radiographic examinations at 5 visits, 3 Magnetic Resonance Imaging (MRI) examinations and 3 DECT procedures at selected sites.

Conditions

Joint Damage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Febuxostat 40 mg or 80 mg

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

Group Type: EXPERIMENTAL

Febuxostat

Intervention Type: DRUG

Febuxostat capsules

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo for Febuxostat

Intervention Type: DRUG

Febuxostat placebo-matching capsules

Interventions

Febuxostat

Febuxostat capsules

Intervention Type: DRUG

Placebo for Febuxostat

Febuxostat placebo-matching capsules

Intervention Type: DRUG

Other Intervention Names

Uloric; TMX-67

Eligibility Criteria

Inclusion Criteria

• 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
• sub-cortical cysts without erosions on x-ray
• joint fluid culture negative for organisms during attacks
• *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.
• Is male and at least 18 years of age OR;

• Female ≥45 years of age and at least 2 years post-menopausal AND has a Follicle Stimulating Hormone (FSH) level ≥40 IU/L OR
• Female receiving hormone replacement therapy (HRT) must be ≥55 years of age (FSH level not required).
• Has hyperuricemia defined as serum Uric Acid (sUA) level ≥7.0 mg/dL at Screening.
• Has a history of ≤2 (1 or 2) flares. In participants with a history of 2 flares, must have had only one flare in any 12 month period. The primary affected joint will be based on the location of the first gout flare which must be located within right or left metatarsophalangeal (MTP), interphalangeal (IP), ankle, metacarpophalangeal (MCP), Proximal Inter-Phalangeal (PIP), or distal inter-phalangeal (DIP) joints prior to Screening.
• Is capable of understanding and complying with protocol requirements, including scheduled clinic procedures.

Exclusion Criteria

• 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.
• Is a study site employee, or is an immediate family member (ie, spouse, parent, child, and sibling) of a study site employee involved in conduct of this study.
• Is unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent form is available.
• Is required to take excluded medications.
• Magnetic Resolution Imaging:

• Has a known hypersensitivity to gadolinium
• Has history of severe asthma
• Has an electronically, magnetically or mechanically activated implanted device
• Has any object that could present a potential hazard or interfere with MRI interpretation secondary to the artifact (i.e. metallic foreign bodies)
• Has a significant medical condition considered by the Investigator (or radiologist) to interfere with the participant's ability to receive gadolinium (eg Sickle cell anemia).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Mesa, Arizona, United States

Tucson, Arizona, United States

Burbank, California, United States

Carmichael, California, United States

Costa Mesa, California, United States

Irvine, California, United States

Orange, California, United States

Rancho Cucamonga, California, United States

San Diego, California, United States

San Luis Obispo, California, United States

Trumbull, Connecticut, United States

Boynton Beach, Florida, United States

Daytona Beach, Florida, United States

Fort Lauderdale, Florida, United States

Hialeah, Florida, United States

Miami, Florida, United States

Sanford, Florida, United States

Tampa, Florida, United States

Winter Park, Florida, United States

Honolulu, Hawaii, United States

Arlington Heights, Illinois, United States

Avon, Indiana, United States

Greenfield, Indiana, United States

Wichita, Kansas, United States

Rockport, Maine, United States

Chaska, Minnesota, United States

Belzoni, Mississippi, United States

Olive Branch, Mississippi, United States

Billings, Montana, United States

Missoula, Montana, United States

Bellevue, Nebraska, United States

Henderson, Nevada, United States

Las Vegas, Nevada, United States

Albuquerque, New Mexico, United States

Charlotte, North Carolina, United States

Lenoir, North Carolina, United States

Shelby, North Carolina, United States

Dayton, Ohio, United States

Franklin, Ohio, United States

Willoughby Hills, Ohio, United States

Oklahoma City, Oklahoma, United States

Eugene, Oregon, United States

Duncansville, Pennsylvania, United States

East Providence, Rhode Island, United States

Columbia, South Carolina, United States

Rapid City, South Dakota, United States

Kingsport, Tennessee, United States

Austin, Texas, United States

Houston, Texas, United States

San Antonio, Texas, United States

Southlake, Texas, United States

Sugar Land, Texas, United States

Arlington, Virginia, United States

Burke, Virginia, United States

Manassas, Virginia, United States

Kenosha, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 28975718 (View on PubMed)

Related Links

http://general.takedapharm.com/content/file.aspx?applicationcode=6C7C39D8-5D09-453B-BF30-696A4AB88E62&fileTypeCode=ULORICPI

Uloric Package Insert

Other Identifiers

U1111-1113-8098

Identifier Type: REGISTRY

Identifier Source: secondary_id

TMX-67_204

Identifier Type: -

Identifier Source: org_study_id