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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Burnaby, British Columbia, Canada
  • Newfoundland and Labrador
    • St. Johns, Newfoundland and Labrador, Canada
  • Ontario
    • London, Ontario, Canada
    • Sarnia, Ontario, Canada
    • Thornhill, Ontario, Canada
    • Toronto, Ontario, Canada
  • Quebec
    • Mirabel, Quebec, Canada
• Georgia
  • Tiblisi, Georgia
• United States
  • California
    • Lincoln, California, United States
    • Los Angeles, California, United States
    • Palo Alto, California, United States
  • Florida
    • Boca Raton, Florida, United States
    • Jacksonville, Florida, United States
    • Miami, Florida, United States
  • Hawaii
    • Honolulu, Hawaii, United States
  • Maryland
    • Baltimore, Maryland, United States
  • Massachusetts
    • Brockton, Massachusetts, United States
  • Missouri
    • St. Louis, Missouri, United States
  • New York
    • Hartsdale, New York, United States
    • New York, New York, United States
  • North Carolina
    • Durham, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Texas
    • San Antonio, Texas, 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:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arhalofenate 400 mg; Arhalofenate 400 mg plus allopurinol 300 mg	Drug: Arhalofenate; Arhalofenate 400 and 600 mgs over-encapsulated tablets once daily for 4 weeks or Allopurinol 300 mg once daily for 4 weeks; Drug: Allopurinol; Allopurinol 300 mg as active comparator; Drug: Colchicine; 0.6 mg colchicine daily as flare prophylaxis
Experimental: Arhalofenate 600 mg; Arhalofenate 600 mg plus allopurinol 300 mg	Drug: Arhalofenate; Arhalofenate 400 and 600 mgs over-encapsulated tablets once daily for 4 weeks or Allopurinol 300 mg once daily for 4 weeks; Drug: Allopurinol; Allopurinol 300 mg as active comparator; Drug: Colchicine; 0.6 mg colchicine daily as flare prophylaxis
Active Comparator: Allopurinol; Placebo plus Allopurinol 300 mg	Drug: Placebo; Placebo; Drug: Allopurinol; Allopurinol 300 mg as active comparator; Drug: Colchicine; 0.6 mg colchicine daily as flare prophylaxis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Uric Acid	Percent change from baseline in serum uric acid in Per Protocol population	Percent change from baseline in serum uric acid at Week 4

Collaborators and Investigators

• Sponsor: CymaBay Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: July 13, 2011
• First Submitted That Met QC Criteria: July 19, 2011
• First Posted (Estimate): July 21, 2011

Study Record Updates

• Last Update Posted (Estimate): September 18, 2015
• Last Update Submitted That Met QC Criteria: September 3, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Hyperuricemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Gout; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Colchicine; Allopurinol
• Other Study ID Numbers: M102-21123