Febuxostat Versus Allopurinol or Placebo in Patients With Hyperuricosuria and Calcium Oxalate Stones
Condition: Hyperuricosuria; Kidney Stones
MeSH terms: Kidney Calculi; Nephrolithiasis
Intervention: Febuxostat; Allopurinol; Placebo
Intervention description: Febuxostat capsules; Allopurinol capsules; Placebo-matching capsules
Intervention MeSH terms: Allopurinol; 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: 99.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Kidney Calculi; Kidney Stones; Nephrolithiasis; Drug Therapy; Uric Acid

Summary:

      The purpose of this study is to determine the efficacy of febuxostat, once daily (QD),
      compared to allopurinol or placebo in patients with excessive amounts of uric acid in their
      urine and who have recently had kidney stones.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has hyperuricosuria, defined as a daily urine uric acid excretion greater than 700 mg
             as measured by 24-hour urine collection prior to randomization.

          -  Has at least one calcium oxalate stone greater than or equal to 3 mm in its longest
             in-plane diameter, identified by Multiple Detector Computated Tomography prior to
             randomization.

          -  Has a recent (within the previous 5 years) history of renal stones prior to screening.

        Exclusion Criteria:

          -  Has gout, secondary hyperuricemia or has experienced a gout flare.

          -  Has a history of xanthinuria.

          -  Has received allopurinol or probenecid within 2 years prior to randomization.

          -  Has received febuxostat.

          -  Has alanine aminotransferase and/or aspartate aminotransferase values greater than 2.0
             times the upper limit of normal at the Screening Visit.

          -  Has an abnormal serum calcium level at the Screening Visit.

          -  Has a significant medical condition and/or conditions that would interfere with the
             treatment, safety or compliance with the protocol according to the judgment of the
             Investigator.

          -  Has a history of drug abuse or a history of alcohol abuse within 5 years prior to the
             Screening Visit.

          -  Participant's measured creatinine clearance is less than 30 mL/min at the Screening
             Visit.

          -  Has hypercalciuria at Screening, while on a regular unrestricted diet, defined as
             urinary excretion of:

               -  greater than 250 mg of calcium/24-hour for females of body weight less than 62.5
                  kg; OR

               -  greater than 300 mg calcium/24-hour for males of body weight less than 75 kg; OR

               -  greater than 4 mg calcium/kg/24-hour for males of body weight greater than or
                  equal 75 kg and females of body weight greater than or equal 62.5 kg.

        EXCLUDED MEDICATIONS:

          -  Febuxostat, allopurinol, probenecid.

          -  Salicylates (chronic use of aspirin ≤325 mg/day is allowed).

          -  Azathioprine.

          -  Mercaptopurine.

          -  Theophylline.

          -  Colchicine.

          -  Pyrazinamide.

          -  Sulfamethoxazole/trimethoprim.

          -  Losartan.

        The following restrictions also apply during the study:

          -  Long-term use (more than 4 continuous weeks) of prescription or over-the-counter
             nonsterioidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors.

          -  If receiving diuretics, participant must have been on a stable dose for at least 30
             days prior to screening. No changes in dosage are allowed during the study.