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

NCT01399008 | Completed Phase 2 Results

• 1 other identifier: M102-21123
• Study Type: interventional
• Target: 100
• Locations: 3 countries
• Sites: 24

Brief Summary

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.

Conditions

Gout

Keywords

Hyperuricemia

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Arhalofenate 400 mg

EXPERIMENTAL

Arhalofenate 400 mg plus allopurinol 300 mg

Drug: Arhalofenate; Drug: Allopurinol; Drug: Colchicine

Arhalofenate 600 mg

EXPERIMENTAL

Arhalofenate 600 mg plus allopurinol 300 mg

Drug: Arhalofenate; Drug: Allopurinol; Drug: Colchicine

Allopurinol

ACTIVE COMPARATOR

Placebo plus Allopurinol 300 mg

Drug: Allopurinol; Drug: Colchicine; Drug: Placebo

Interventions

Arhalofenate DRUG

Arhalofenate 400 and 600 mgs over-encapsulated tablets once daily for 4 weeks or Allopurinol 300 mg once daily for 4 weeks

Arhalofenate 400 mg; Arhalofenate 600 mg

Allopurinol DRUG

Allopurinol 300 mg as active comparator

Allopurinol; Arhalofenate 400 mg; Arhalofenate 600 mg

Colchicine DRUG

0.6 mg colchicine daily as flare prophylaxis

Allopurinol; Arhalofenate 400 mg; Arhalofenate 600 mg

Placebo DRUG

Placebo

Allopurinol

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Known gout patients (per criteria of the American Rheumatism Association for the classification of the acute arthritis of primary gout
• 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 -
• 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.
• Male or female, 18-75 years of age at screening
• 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.
• Female patients must not be pregnant or lactating.
• 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.
• Estimated creatinine clearance (CrCl) by Cockcroft-Gault method ≥ 60 mL/min at screening
• Serum creatinine value ≤ 1.1 mg/dL in females and ≤ 1.3 mg/dL in males
• 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.
• 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

You may not qualify if:

• Treatment with any ULT other than allopurinol (e.g., probenecid, benzbromarone, febuxostat, or pegloticase) within 30 days of the Screening Visit
• Known or suspected secondary hyperuricemia (e.g. due to myeloproliferative disorder, or organ transplant)
• Diagnosis of xanthinuria
• History of documented or suspected kidney stones
• Known infection with HIV or history of viral hepatitis type B or C
• History of illicit drug or alcohol abuse within 1 year of screening
• 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
• 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
• Malignancy (except treated basal cell carcinoma) within five years of screening
• BMI \> 42 kg/m2
• Current or expected requirement for anticoagulant therapy (except for aspirin ≤ 325 mg/day)
• Rheumatoid arthritis or other autoimmune disease requiring ongoing treatment
• 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
• Chronic treatment with 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 flare

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (24)

Unknown Facility

Lincoln, California, United States

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Los Angeles, California, United States

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Palo Alto, California, United States

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Boca Raton, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Honolulu, Hawaii, United States

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Baltimore, Maryland, United States

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Brockton, Massachusetts, United States

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St Louis, Missouri, United States

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Hartsdale, New York, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Cincinnati, Ohio, United States

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San Antonio, Texas, United States

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West Jordan, Utah, United States

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Burnaby, British Columbia, Canada

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St. John's, Newfoundland and Labrador, Canada

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London, Ontario, Canada

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Sarnia, Ontario, Canada

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Thornhill, Ontario, Canada

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Toronto, Ontario, Canada

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Mirabel, Quebec, Canada

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Tbilisi, Georgia

Location

MeSH Terms

Conditions

Gout; Hyperuricemia

Interventions

arhalofenate; Allopurinol; Colchicine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Alkaloids

Results Point of Contact

• Title: Mary Jean Stempien, M.D., Acting Chief Medical Officer
• Organization: Metabolex

mjstempien@metabolex.com

510-293-8800

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2011
• First Posted: July 21, 2011
• Study Start: June 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: September 18, 2015
• Results First Posted: July 28, 2014

Record last verified: 2015-09

Locations

US (16); CA (7); GE (1)