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

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

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.

Study Overview

• Status: Completed
• Conditions: Hyperuricemia; Gout
• Intervention / Treatment: Drug: Arhalofenate; Drug: Arhalofenate; Drug: Colchicine; Drug: Placebo comparator

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States
  • California
    • Los Angeles, California, United States
  • Florida
    • Boca Raton, Florida, United States
    • Jupiter, Florida, United States
    • Tampa, Florida, United States
  • Hawaii
    • Honolulu, Hawaii, United States
  • Maryland
    • Wheaton, Maryland, United States
  • Missouri
    • St. Louis, Missouri, United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Raleigh, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Utah
    • West Jordan, Utah, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Colchicine; 0.6 mg colchicine daily for flare prophylaxis; Drug: Placebo comparator; Matching placebo once daily for 4 weeks
EXPERIMENTAL: Arhalofenate 400 mg	Drug: Arhalofenate; Arhalofenate 400 mg once daily for 4 weeks; Other Names: MBX-102; Drug: Arhalofenate; Arhalofenate 600 mg once daily for 4 weeks; Other Names: MBX-102; Drug: Colchicine; 0.6 mg colchicine daily for flare prophylaxis
EXPERIMENTAL: Arhalofenate 600 mg	Drug: Arhalofenate; Arhalofenate 400 mg once daily for 4 weeks; Other Names: MBX-102; Drug: Arhalofenate; Arhalofenate 600 mg once daily for 4 weeks; Other Names: MBX-102; Drug: Colchicine; 0.6 mg colchicine daily for flare prophylaxis

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: CymaBay Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (ACTUAL): November 1, 2011
• Study Completion (ACTUAL): November 1, 2011

Study Registration Dates

• First Submitted: April 14, 2011
• First Submitted That Met QC Criteria: April 15, 2011
• First Posted (ESTIMATE): April 18, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): April 17, 2015
• Last Update Submitted That Met QC Criteria: March 30, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Hyperuricemia; Gout; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: M102-21122