Effect of Febuxostat on Joint Damage in Hyperuricemic Subjects With Early Gout
Condition: Joint Damage
MeSH terms: Hyperuricemia
Intervention: Febuxostat; Placebo for Febuxostat
Intervention description: Febuxostat capsules; Febuxostat placebo-matching capsules
Intervention MeSH terms: Febuxostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 314.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gout; Hyperuricemia; Uric Acid; Drug Therapy

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.
    

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).