A Phase 4 Safety and Efficacy Study to Evaluate Lesinurad 200 mg in Participants With Gout and Renal Impairment
Condition: Gout; Chronic Kidney Disease (CKD)
MeSH terms: Gout; Kidney Diseases; Renal Insufficiency, Chronic
Intervention: Lesinurad; XOI; Placebo; colchicine; corticosteroids
Intervention description: 200 mg oral tablet; All participants must be on a stable, medically appropriate dose of XOI as their sole urate-lowering therapy (ULT) indicated for the treatment of gout for at least 4 weeks prior to Screening and throughout the Screening Period. This stable dose of XOI will be maintained throughout the study period.; matching placebo oral tablet; Gout flare prophylaxis: commercially available colchicine is provided through the Month 6 study visit. Actual colchicine dose (0.5 or 0.6 mg qd) and frequency were adjusted based on the local label, subject medical history, and clinical judgement.; Gout flare prophylaxis: Participants unable to take colchicine are permitted to take a short course of low-dose oral corticosteroids up to the Month 3 study visit
Intervention MeSH terms: Colchicine; Allopurinol; Febuxostat; Lesinurad
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, Double-Blind, Multicenter, Placebo-Controlled
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: active vs placebo visually identical tablets
Enrollment: 242.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This study evaluates the safety and efficacy of lesinurad administered with an XOI versus a
      placebo plus an XOI in gout participants who have moderate renal impairment and who are not
      at target level of serum urate (sUA).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject is able to understand the study procedures, the risks involved, and willing to
             provide written informed consent before the first study related activity.

          2. Subject is willing to adhere to the protocol schedule.

          3. Subject is ≥ 18 years and ≤ 85 years of age.

          4. Subject has a diagnosis of gout.

          5. Subject has moderate renal impairment with estimated creatinine clearance (eCrCl;
             calculated by the Cockcroft-Gault formula using ideal body weight) 25.0 to ≤ 65.0
             mL/min at Screening Visits 1 and 2 and an average eCrCl for both screening visits of
             30.0 to < 60.0 mL/min.

          6. Subject has been taking an XOI as ULT indicated for the treatment of gout for at least
             4 weeks prior to Screening at a stable, medically appropriate dose, as determined by
             the Investigator. The minimum dose of allopurinol is 200 mg daily, and the minimum
             dose of febuxostat is the lowest approved dose per the local product label.

          7. Subject has a serum uric acid level ≥ 6.0 mg/dL (357 µmol/L) at Screening Visits 1 and
             2.

          8. Subject is male or female; females must not be pregnant or breastfeeding and females
             of childbearing potential must agree to use nonhormonal contraception during the
             Screening Period and while taking investigation product (IP).

          9. Subject has a body mass index < 45 kg/m^2.

        Exclusion Criteria:

          1. Subject had unstable angina, New York Heart Association class III or IV heart failure,
             myocardial infarction, or stroke within the last 6 months prior to randomization; or
             had a deep venous thrombosis within the previous 3 months prior to randomization.

          2. Subject has uncontrolled hypertension (defined as systolic pressure above 160 or
             diastolic pressure above 95 mm Hg at either Screening Visits 1 or 2).

          3. Subject has severe hepatic impairment (defined as Child-Pugh Class C) or is known
             human immunodeficiency virus (HIV) positive.

          4. Subject is a solid organ transplant recipient.

          5. Subject has a urine protein of 3+ or higher by dipstick by the central laboratory at
             Screening Visit 2.

          6. Subject has a history of glomerulonephritis.

          7. Subject is taking valpromide, progabide, valproic acid, or other known inhibitors of
             epoxide hydrolase, or subject is taking ranolazine, cyclosporine, azathioprine or
             mercaptopurine.

          8. Subject is receiving chronic treatment with more than 325 mg of salicylates per day.

          9. Subject is unable to initiate gout flare prophylaxis with colchicine or low-dose oral
             corticosteroids at Baseline.

         10. Subject is taking any other drug approved for use as a urate-lowering medication other
             than allopurinol or febuxostat (eg, pegloticase, probenecid, benzbromarone) within 4
             weeks prior to Screening or during Screening.

         11. For subjects who will be taking colchicine for gout flare prophylaxis: Subject is
             taking, or anticipated to take during the first 6 months on study, moderate or strong
             Cytochrome P450 3A4 (CYP3A4) inhibitors (ie, verapamil or diltiazem, clarithromycin,
             and fluconazole; or grapefruit or grapefruit juice).

         12. Subject previously participated in a clinical study involving lesinurad (RDEA594) or
             verinurad (RDEA3170) and received active treatment or placebo, or has taken
             commercially-available lesinurad.

         13. Subject has a gout flare during the Screening Period.

         14. Subject is pregnant or breastfeeding.

         15. Subject consumes more than 14 drinks of alcohol per week (eg, 1 drink = 5 oz [150 mL]
             of wine, 12 oz [360 mL] of beer, or 1.5 oz [45 mL] of hard liquor).

         16. Subject has a history of malignancy and has been on active treatment within the
             previous 5 years prior to randomization with the exception of non-melanoma skin
             cancer, treated in situ Grade 1 cervical cancer, or treated ductal carcinoma in situ
             of the breast.

         17. Subject has been hospitalized (other than for elective surgery) or received
             intravenous contrast (eg, for computerized tomography (CT) scan or any angiography)
             within 1 month prior to Screening or during Screening.

         18. Subject has participated in a clinical trial within 8 weeks prior to Screening.

         19. Subject has any other medical or psychological condition, which in the opinion of the
             Investigator might create undue risk to the subject or interfere with the subject's
             ability to comply with the protocol requirements or to complete the study.

         20. The maximum number of subjects in the eCrCl stratification subgroup has been reached.