Efficacy and Safety of Extended Release and Immediate Release Febuxostat in Participants With Gout and Moderate Renal Impairment
Condition: Gout; Moderate Renal Impairment
MeSH terms: Gout; Renal Insufficiency
Intervention: Febuxostat IR; Febuxostat XR; Febuxostat placebo; Colchicine; Naproxen; Lansoprazole
Intervention description: Febuxostat IR over-encapsulated tablets; Febuxostat over-encapsulated capsules; Febuxostat IR and XR placebo-matching capsules; Colchicine tablets; Naproxen tablets; Lansoprazole capsules
Intervention MeSH terms: Naproxen; Colchicine; Febuxostat; Lansoprazole; Dexlansoprazole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 189.0
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 gout participants with moderate renal impairment.
    

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) [Modification of Diet in Renal
             Disease (MDRD)] ≥30 mL/min and <60 mL/min at 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 dependant 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 either a myocardial infarction (MI), stroke, hospitalized unstable
             angina, cardiac or cerebrovascular revascularization procedure or hospitalized
             transient ischemic attack (TIA).

         14. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
             abuse within 5 years prior to the Screening visit. Participant consumes >14 alcoholic
             beverages/week.

         15. Has participated in another investigational study within the 30 days prior to the
             Screening Visit.

         16. Has a known history of infection with hepatitis B, hepatitis C, or human
             immunodeficiency virus.

         17. Is required to take excluded medications.