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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CymaBay Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01399008
First received: July 13, 2011
Last updated: July 2, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Gout
Drug: Arhalofenate
Drug: Allopurinol
Drug: Colchicine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by CymaBay Therapeutics, Inc.:

Primary Outcome Measures:
  • Serum Uric Acid [ Time Frame: Percent change from baseline in serum uric acid at Week 4 ] [ Designated as safety issue: No ]
    Percent change from baseline in serum uric acid in Per Protocol population


Enrollment: 100
Study Start Date: June 2011
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Allopurinol
Allopurinol 300 mg as active comparator
Drug: Colchicine
0.6 mg colchicine daily as flare prophylaxis
Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01399008

  Show 24 Study Locations
Sponsors and Collaborators
CymaBay Therapeutics, Inc.
  More Information

No publications provided

Responsible Party: CymaBay Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01399008     History of Changes
Other Study ID Numbers: M102-21123
Study First Received: July 13, 2011
Results First Received: March 20, 2014
Last Updated: July 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by CymaBay Therapeutics, Inc.:
Hyperuricemia

Additional relevant MeSH terms:
Gout
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Allopurinol
Colchicine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Protective Agents
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 28, 2014