Safety/Efficacy Study to Evaluate of MBX-102 in Combination With Allopurinol in Gout Patients
Condition: Gout
MeSH terms: Gout
Intervention: Arhalofenate; Allopurinol; Colchicine; Placebo
Intervention description: Arhalofenate 400 and 600 mgs over-encapsulated tablets once daily for 4 weeks or Allopurinol 300 mg once daily for 4 weeks; Allopurinol 300 mg as active comparator; 0.6 mg colchicine daily as flare prophylaxis; Placebo
Intervention MeSH terms: Colchicine; Allopurinol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Hyperuricemia

Summary:

      The purpose of this study is to evaluate the efficacy, safety and tolerability of MBX-102 in
      combination with allopurinol compared to allopurinol alone when administered orally once a
      day for four weeks to gout patients with an inadequate hypouricemic response to allopurinol
      alone.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Known gout patients (per criteria of the American Rheumatism Association for the
             classification of the acute arthritis of primary gout

               1. Patients who have been taking at least 200 mg/day of allopurinol as the sole ULT
                  for at least two weeks with a sUA of ≥ 6.5 mg/dL and ≤ 12 mg/dL at screening and
                  ≥ 6.0 mg/dL and ≤ 12 mg/dL at Week -1 (Visit 2) randomization visit.

                  -OR -

               2. Patients who are not on ULT or are taking allopurinol < 200 mg/day must have a
                  sUA ≥ 8.0 mg/dL and ≤ 12 mg/dL at screening and ≥ 6.0 mg/dL and ≤ 12 mg/dL at
                  Week -1 (Visit 2) randomization visit.

          2. Male or female, 18-75 years of age at screening

          3. All female patients must be surgically sterile or post-menopausal (at least 45 years
             of age with no history of menses for at least 2 years; or any age with no history of
             menses for at least six months and serum FSH ≥ 40 mIU/mL) or have a partner who has
             undergone vasectomy or must agree to use two medically accepted methods of
             contraception including a barrier method (see the list in Appendix 4) for the entire
             duration of the study unless she reports complete sexual abstinence.

          4. Female patients must not be pregnant or lactating.

          5. Male patients with a female partner of child-bearing potential must agree to use
             condoms or the partner must use a medically acceptable method of contraception for the
             entire duration of the study.

          6. Estimated creatinine clearance (CrCl) by Cockcroft-Gault method ≥ 60 mL/min at
             screening

          7. Serum creatinine value ≤ 1.1 mg/dL in females and ≤ 1.3 mg/dL in males

          8. Liver function tests ≤ 1.5X ULN for AST, ALT and T-bilirubin, ≤ 2X ULN for ALP, ≤ 3X
             ULN for GGT; and ≤ 3X ULN for CK

          9. All other clinical laboratory parameters must be within normal limits or considered
             not clinically significant for participation in this study.

         10. Electrocardiogram (ECG) must be normal, or if abnormal, considered not clinically
             significant for participation in this study.

         11. Systolic blood pressure ≤ 160 mm Hg and diastolic blood pressure ≤ 90 mm Hg; known
             hypertensive patients controlled with medications other than thiazide diuretics (blood
             pressure [BP] reading as above) may be included

        Exclusion Criteria:

          1. Treatment with any ULT other than allopurinol (e.g., probenecid, benzbromarone,
             febuxostat, or pegloticase) within 30 days of the Screening Visit

          2. Known or suspected secondary hyperuricemia (e.g. due to myeloproliferative disorder,
             or organ transplant)

          3. Diagnosis of xanthinuria

          4. History of documented or suspected kidney stones

          5. Known infection with HIV or history of viral hepatitis type B or C

          6. History of illicit drug or alcohol abuse within 1 year of screening

          7. History of significant pulmonary disease, upper GI bleeding, documented peptic ulcer
             disease (unless known H. pylori infection treated successfully without recurrence), or
             nephrotic syndrome within three years of screening

          8. History of stroke, TIA, acute MI, congestive heart failure (NYHA Class II-IV), angina
             pectoris, coronary intervention procedure (including but not limited to angioplasty,
             stent placement, coronary revascularization), lower extremity bypass procedure,
             systemic or intracoronary fibrinolytic therapy within five years of screening

          9. Malignancy (except treated basal cell carcinoma) within five years of screening

         10. BMI > 42 kg/m2

         11. Current or expected requirement for anticoagulant therapy (except for aspirin ≤ 325
             mg/day)

         12. Rheumatoid arthritis or other autoimmune disease requiring ongoing treatment

         13. Current or expected treatment with potent CYP3A4 inhibitors (See Appendix 6),
             cytotoxic agents (azathioprine, mercaptopurine, cyclosporine, cyclophosphamide, etc.),
             ranolazine, digoxin, theophylline, sulphonylureas, thiazolidinediones, diuretics,
             atypical antipsychotic agents, ampicillin, amoxicillin or phenytoin

         14. Chronic treatment with NSAIDs (use to treat acute flares are permitted).

         15. Current or expected treatment with systemic corticosteroids (except topical,
             ophthalmic, intra-articular, or inhaled at a dose < 1600 μg/day) other than to treat
             acute flare

         16. Known hypersensitivity to allopurinol, colchicine, or aspirin

         17. Treatment with any other investigational therapy within the 30 days prior to
             screening, or patients who received at least one dose of study drug while enrolled in
             any previous or concomitant MBX-102 trial

         18. Any other condition that compromises the ability of the patient to provide informed
             consent or to comply with the objectives and procedures of this protocol, as judged by
             the investigator and/or medical monitor.