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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01078389
First received: February 26, 2010
Last updated: September 24, 2013
Last verified: September 2013
  Purpose

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


Condition Intervention Phase
Joint Damage
Drug: Febuxostat
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Phase 2 Study to Evaluate the Effect of Febuxostat Versus Placebo in Joint Damage in Hyperuricemic Subjects With Early Gout

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Mean Change from Baseline to Month 24 in a modified Sharp/van der Heijde Erosion Score of the single affected joint. [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean Change from Baseline to Month 24 in the modified Sharp/van der Heijde Total Scores from full hand and foot radiographs. [ Time Frame: Baseline and Month 24. ] [ Designated as safety issue: No ]
  • Mean Change from Baseline to Month 24 in the modified Sharp/van der Heijde Erosion Scores from full hand and foot radiographs. [ Time Frame: Baseline and Month 24. ] [ Designated as safety issue: No ]
  • Mean change from baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) score. [ Time Frame: Baseline and Month 24. ] [ Designated as safety issue: No ]
  • Mean change from baseline to Month 24 in a modified Sharp/van der Heijde Total Score of the single affected joint. [ Time Frame: Baseline and Month 24. ] [ Designated as safety issue: No ]

Enrollment: 314
Study Start Date: March 2010
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Febuxostat 40 mg or 80 mg QD
(based on serum urate levels)
Drug: Febuxostat
Febuxostat 40 mg or 80 mg (based on serum urate levels), capsules, orally, once daily for up to 24 Months.
Other Names:
  • Uloric
  • TMX-67
Placebo Comparator: Placebo QD Drug: Placebo
Placebo-matching capsules, orally, once daily for up to 24 Months.

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 subjects with gout.

Current treatments focus on initiating urate-lowering therapy in hyperuricemic gout patients who have experienced 3 or more 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

This study will evaluate the effect of febuxostat on joint damage in hyperuricemic subjects with early gout. All subjects 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 Erosion scoring method (named after Dr. Sharp) has been validated in subjects with chronic gout and will be used in this study for evaluating 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have a history or presence of gout as defined by the American Rheumatism Association preliminary criteria for the diagnosis of gout and have experienced only one gout flare
  • Has hyperuricemia at Screening
  • Has a history of (one) single acute gout flare prior to Screening

Exclusion Criteria:

  • Previously on Urate-lowering therapy (allopurinol, febuxostat or probenecid)
  • Has secondary hyperuricemia.
  • Has a history of xanthinuria
  • Has a known hypersensitivity to any component of the febuxostat formulation
  • Has rheumatoid arthritis
  • 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 and/or aspartate aminotransferase 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 an estimated creatinine clearance less than 60 mL/min
  • 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
  • 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 subject's ability to receive gadolinium
  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: NCT01078389

  Show 56 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

Additional Information:
No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01078389     History of Changes
Other Study ID Numbers: TMX-67_204, U1111-1113-8098
Study First Received: February 26, 2010
Last Updated: September 24, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Gout
Hyperuricemia
Uric Acid
Drug Therapy

Additional relevant MeSH terms:
Hyperuricemia
Pathologic Processes
Febuxostat
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014