Safety/Efficacy Study to Evaluate of MBX-102 in Combination With Allopurinol in Gout Patients

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of MBX-102 in Combination With Allopurinol in Gout Patients With an Inadequate Hypouricemic Response to Allopurinol Alone

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.

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.