Safety and Efficacy Study of MBX-102 in Treatment of Hyperuricemia in Patients With Gout

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the safety and effectiveness of MBX-102 compared to placebo when given orally once daily for 4 weeks for the treatment of hyperuricemia in patients with gout.

Official Title
-----------------
A Phase 2 Randomized Double-Blind Placebo-Controlled Study to Evaluate the Safety and Efficacy of MBX-102 in the Treatment of Hyperuricemia in Patients With Gout

Conditions
-----------------
Hyperuricemia, Gout

Intervention / Treatment
-----------------
* Drug: Arhalofenate
* Drug: Arhalofenate
* Drug: Placebo comparator
* Drug: Colchicine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Read and sign the informed consent after the elements of consent have been fully explained and all questions have been addressed, prior to any study procedures. Known gout patient (per criteria of the American Rheumatism Association for the classification of the acute arthritis of primary gout in Appendix 3) the sUA must be ≥ 8.0 mg/dL and ≤12 mg/dL if on ULT, the patients must agree to temporarily discontinue their existing ULT and the sUA must be ≥ 8.0 mg/dL and ≤12 mg/dL after wash-out at Week -1 Male or female, 18-75 years of age at Screening Visit 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 6 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 reporting complete sexual abstinence. Female patients must not be pregnant or lactating Male patients with a female partner of child-bearing potential must agree to use condom or the partner must use a medically acceptable method of contraception for the entire duration of the study. Patients must have an estimated CrCl ≥ 60 mL/min as calculated by the Cockcroft-Gault method Serum creatinine value must be ≤ 1.1 mg/dL in females and ≤ 1.3 mg/dL in males Patients must have 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 All other clinical laboratory parameters must be within normal limits or considered not clinically significant for participation in this study Electrocardiogram (ECG) must be normal, or if abnormal, considered not clinically significant for participation in this study Patients must have a systolic blood pressure ≤ 160 mm Hg and a diastolic blood pressure ≤ 90 mm Hg; known hypertensive patients controlled with medication other than thiazide diuretics (BP reading as above) may be included Exclusion Criteria: Known or suspected secondary hyperuricemia (e.g. due to myeloproliferative disorder, or organ transplant). Known patient with xanthinuria History of documented or suspected kidney stones Over producers of uric acid as evidenced by 24-hour urinary uric acid > 800 mg (on normal unrestricted diet) Known infection with the human immunodeficiency virus (HIV) or history of viral hepatitis type B or C History of illicit drug or alcohol abuse within last 1 year 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 last 3 years All patients must not have had a stroke, TIA, acute myocardial infarction, 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 last 5 years Malignancy within the last 5 years (except resected basal cell carcinoma) Body mass index (BMI) > 42 kg/m2 Current or expected requirement for anticoagulant therapy (except for ≤ 325 mg/day aspirin and/or Plavix® 75 mg/day) Rheumatoid arthritis or other autoimmune disease requiring ongoing treatment Current or expected treatment with potent CYP3A4 inhibitors (See in Appendix 6), ranolazine, digoxin, cyclosporine, cyclophosphamide and other cytotoxic agents, sulphonylurea, thiazolidinedione, diuretic, atypical antipsychotic agents, and phenytoin Chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs use to treat acute flares are permitted) 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 flares Known hypersensitivity to colchicine Treatment with any other investigational therapy within the 30 days prior to the Screening Visit, or patients who received at least one dose of blinded study drug while enrolled in any previous MBX-102 trial 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arhalofenate 400 mg<br> | Drug: Arhalofenate<br>* Arhalofenate 400 mg once daily for 4 weeks<br>* Other names: MBX-102;Drug: Colchicine<br>* 0.6 mg colchicine daily for flare prophylaxis<br>|
| Experimental: Arhalofenate 600 mg<br> | Drug: Arhalofenate<br>* Arhalofenate 600 mg once daily for 4 weeks<br>* Other names: MBX-102;Drug: Colchicine<br>* 0.6 mg colchicine daily for flare prophylaxis<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo comparator<br>* Matching placebo once daily for 4 weeks<br>Drug: Colchicine<br>* 0.6 mg colchicine daily for flare prophylaxis<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum uric acid |  | Baseline and end of treatment phase (4 wks) |