Efficacy and Safety of Extended Release and Immediate Release Febuxostat in Participants With Gout
Condition: Gout
MeSH terms: Gout
Intervention: Febuxostat IR; Febuxostat XR; Febuxostat placebo; Colchicine; Naproxen; Lansoprazole
Intervention description: Febuxostat IR over-encapsulated tablets; Febuxostat XR over-encapsulated capsules; Febuxostat placebo-matching capsules; Colchicine tablets; Naproxen tablets; Lansoprazole capsules
Intervention MeSH terms: Naproxen; Colchicine; Febuxostat; Lansoprazole; Dexlansoprazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1790.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purpose of this study is to evaluate the efficacy and safety of febuxostat 40 mg extended
      release (XR) and 80 mg XR in comparison with febuxostat 40 mg immediate release (IR) and 80
      mg IR, respectively, in participants with gout.
    

Eligibility criteria:

        Inclusion Criteria:

          1. In the opinion of the investigator, the participant is capable of understanding and
             complying with protocol requirements.

          2. The participant or, when applicable, the participant's legally acceptable
             representative signs and dates a written, informed consent form and any required
             privacy authorization prior to the initiation of any study procedure.

          3. Has a history or presence of gout defined as having one or more of the American
             Rheumatism Association (ARA) criteria for the diagnosis of gout:

               1. A tophus proven to contain urate crystals by chemical or polarized light
                  microscopic means, AND/OR;

               2. Characteristic urate crystals in the joint fluid, AND/OR;

               3. History of at least 6 of the following clinical, laboratory, and x-ray phenomena:

             i. more than one attack of acute arthritis, ii. maximum inflammation developed within
             1 day, iii. monoarticular arthritis, iv. redness observed over joints, v. first
             metatarsophalangeal joint painful or swollen, vi. unilateral first metatarsophalangeal
             joint attack, vii. unilateral tarsal joint attack, viii. tophus (proven or suspected),
             ix. Hyperuricemia, x. asymmetric swelling within a joint on x-ray, xi. subcortical
             cysts without erosions on x-ray; xii. joint fluid culture negative for organisms
             during attack.

          4. Is male or female at least 18 years of age, inclusive.

          5. A female participant of childbearing potential who is sexually active with a
             nonsterilized male partner agrees to use routinely adequate contraception from signing
             of informed consent throughout the duration of the study.

          6. Have a serum urate (sUA) level ≥8.0 mg/dL at the Day -4 Visit or at the retest visit.

          7. Has an estimated Glomerular Filtration Rate (eGRF) ≥15 mL/min using the Modification
             of Diet in Renal Disease (MDRD) formula at the Screening visit (Day -21 for
             participants on urate lowering therapy (ULT) and Day -4 for participants not on ULT)
             or at the retest visit.

          8. Has at least one gout flare within 12 months prior to Screening visit.

        Exclusion Criteria:

          1. Has received any investigational compound within 30 days prior to Screening.

          2. Is an immediate family member, study site employee, or is in a dependent relationship
             with a study site employee who is involved in conduct of this study (eg, spouse,
             parent, child, sibling) or may consent under duress.

          3. Is breastfeeding or pregnant.

          4. Has secondary hyperuricemia (eg, due to myeloproliferative disorder).

          5. Has a history of xanthinuria.

          6. Has received ULT (ie, allopurinol, probenecid, etc.) within 20 days prior to Day
             1/Randomization Visit.

          7. Has a known hypersensitivity to febuxostat or any components of their formulation; has
             a known hypersensitivity to naproxen, any other nonsteroidal anti-inflammatory drug
             (NSAID), aspirin, lansoprazole, colchicine or any components in their formulation.

          8. Has active peptic ulcer disease.

          9. Has a history of cancer (other than basal cell carcinoma of the skin) within 5 years
             prior to the Screening Visit.

         10. Has alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values >2 x
             the upper limit of normal (ULN).

         11. Has rheumatoid arthritis which requires treatment.

         12. Has a significant medical condition and/or conditions that would interfere with the
             treatment, safety, or compliance with the protocol.

         13. Has experienced a myocardial infarction (MI), stroke, hospitalized unstable angina,
             cardiac or cerebrovascular revascularization procedure or hospitalized transient
             ischemic attack (TIA) - except in participants who have severe renal impairment.

         14. Participants with severe renal impairment had a MI or stroke within 90 days prior to
             initial screening visit or has a MI or stroke during the screening period prior to Day
             1/Randomization Visit.

         15. Participant consumes >14 alcoholic beverages/week. Has a history of alcoholism or
             illicit drug abuse within 5 years.

         16. Has participated in another investigational study within the 30 days prior to the
             Screening Visit.

         17. Has a known history of infection with hepatitis B, hepatitis C, or human
             immunodeficiency virus.

         18. Is required to take excluded medications.