Evaluate the Efficacy and Safety of Arhalofenate for Preventing Flares and Reducing Serum Uric Acid in Gout Patients

NCT02063997 | Completed Phase 2

• 1 other identifier: CB102-21425
• Study Type: interventional
• Target: 248
• Locations: 3 countries
• Sites: 56

Brief Summary

The purpose of this study is to determine whether arhalofenate is effective in preventing flares and reducing serum uric acid in gout patients.

Conditions

Gout

Outcome Measures

Primary Outcomes (1)

• The incidence of flares (mean number of flares per patient) from baseline through Week 12 in the arhalofenate 800 mg group compared to the allopurinol 300 mg group.

  12 weeks

Secondary Outcomes (7)

• Percent sUA reduction from baseline to Week 12 in the arhalofenate 800 mg group compared to the placebo group

  12 weeks

• Percent sUA reduction from baseline to Week 12 in the arhalofenate 600 mg group compared to the placebo group

  12 weeks

• Proportion of patients with sUA < 6 mg/dL at Week 12 in the arhalofenate 800 mg group compared to the placebo group

  12 weeks

• The incidence of flares from baseline through Week 12 in the arhalofenate 600 mg group compared to the allopurinol 300 mg group

  12 weeks

• Proportion of patients with sUA < 6 mg/dL at Week 12 in the arhalofenate 600 mg group compared to placebo group

  12 weeks

Other Outcomes (14)

• Proportion of patients experiencing at least one flare from baseline through Week 12

  12 weeks

• Proportion of patients experiencing two or more flares from baseline through Week 12

  12 weeks

• The incidence of flares from baseline through Week 4, from Week 5 through Week 8, and from Week 9 through Week 12

  12 weeks

Study Arms (5)

Arhalofenate 600 mg

EXPERIMENTAL

Drug: Arhalofenate 600 mg

Arhalofenate 800 mg

EXPERIMENTAL

Drug: Arhalofenate 800 mg

Allopurinol 300 mg; colchicine 0.6 mg

ACTIVE COMPARATOR

Drug: Allopurinol 300 mg; Drug: Colchicine 0.6 mg

Allopurinol 300 mg

ACTIVE COMPARATOR

Drug: Allopurinol 300 mg

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Arhalofenate 600 mg DRUG

Arhalofenate 600 mg tablets once daily for 12 weeks

Arhalofenate 600 mg

Allopurinol 300 mg DRUG

Allopurinol 300 mg tablets once daily for 12 weeks

Allopurinol 300 mg; Allopurinol 300 mg; colchicine 0.6 mg

Colchicine 0.6 mg DRUG

Colchicine 0.6 mg over-encapsulated tablets once daily for 12 weeks

Allopurinol 300 mg; colchicine 0.6 mg

Placebo DRUG

Placebo tablets once daily for 12 weeks

Placebo

Arhalofenate 800 mg DRUG

Arhalofenate 800 mg tablets once daily for 12 weeks

Arhalofenate 800 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients between 18 and 75 years of age, inclusive
• Known gout diagnosis (per criteria of the American Rheumatism Association for the classification of the acute arthritis of primary gout, see Appendix 3)
• At least three patient-reported and documented flares during the 12 months prior to screening (the first of these flares may have resulted in the gout diagnosis; any recent flare must have resolved, with the patient back to usual comfort level at least seven days prior to screening)
• Have not used any ULT since at least two weeks prior to screening
• Have not used colchicine since at least two weeks prior to screening
• Usual level of resting pain when NOT experiencing flare is three or less on an 11-point numerical rating scale (NRS)
• Have a sUA ≥ 7.5 mg/dL and ≤ 12 mg/dL 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 two years); or have a partner who has undergone vasectomy or must agree to use two medically accepted methods of contraception including a barrier method (see Appendix 4) for the entire duration of study participation unless she reports complete sexual abstinence. Female patients must not be pregnant or lactating
• Estimated creatinine clearance (eCrCl) ≥ 60 ml/min/1.73m2 calculated by Cockcroft-Gault method at screening
• Liver function tests ≤ 3X ULN for AST, ALT and total bilirubin; ≤ 3X ULN for ALP and GGT; and ≤ 3X ULN for CK at screening
• All other clinical laboratory parameters must be within normal limits or considered not clinically significant
• Electrocardiogram (ECG) must be normal, or if abnormal, considered not clinically significant at screening
• Systolic blood pressure ≤ 160 mm Hg and diastolic blood pressure ≤ 90 mm Hg at screening; known hypertensive patients stable (blood pressure \[BP\] reading as above) with medication may be included
• Patients using agents known to influence sUA levels (see Appendix 7) must be on a stable dose and regimen for at least two weeks prior to screening and must be willing to continue the same doses and regimens during study participation
• Expected to be able to tolerate a short course of either oral NSAIDs and/or oral steroids as may be needed to treat a flare

You may not qualify if:

• Receiving treatment with allopurinol, colchicine, probenecid, benzbromarone, or febuxostat within two weeks or pegloticase within six months prior to screening
• Known or suspected secondary hyperuricemia (e.g. due to myeloproliferative disorder or organ transplant)
• Diagnosis of xanthinuria
• Fractional excretion of urate \> 10% at screening
• History of documented or suspected kidney stones
• Known infection with the human immunodeficiency virus (HIV) or history of viral hepatitis type B or C
• A diagnosis of illicit drug or alcohol dependence or abuse within one year of screening
• History of upper gastrointestinal (GI) bleeding, documented peptic ulcer disease (unless known H. pylori infection treated successfully without recurrence), within three years of screening
• History of stroke, transient ischemic attack (TIA), acute myocardial infarction (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
• History of cancer within five years of screening, with the following exceptions: adequately treated non-melanomatous skin cancers, non-metastatic prostate cancer or in situ cervical cancer
• Patients with a history of bladder cancer, active bladder cancer or hematuria
• Body mass index (BMI) \> 42 kg/m2 at screening
• Current or expected requirement for anticoagulant therapy (except for aspirin ≤ 325 mg/day, clopidogrel \[Plavix\] ≤ 75 mg/day, or prasugrel \[Effient\] ≤ 10 mg/day)
• Use of any of the following within eight weeks prior to screening: potent CYP3A4 inhibitors, cytotoxic agents (including azathioprine, mercaptopurine, cyclosporine, cyclophosphamide, etc.), ranolazine, digoxin, theophylline, sulphonylureas, thiazolidinediones (e.g., rosiglitazone or pioglitazone), atypical antipsychotic agents, ampicillin, amoxicillin, loop diuretics or phenytoin
• Chronic treatment with NSAIDs (except for as needed \[prn\] use to treat acute events); per protocol a short course of oral NSAIDs may be used to treat flares during the study

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (56)

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Birmingham, Alabama, United States

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Scottsdale, Arizona, United States

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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El Cajon, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Denver, Colorado, United States

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Washington D.C., District of Columbia, United States

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Clearwater, Florida, United States

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DeLand, Florida, United States

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Jupiter, Florida, United States

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New Port Richey, Florida, United States

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Orlando, Florida, United States

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Palm Harbor, Florida, United States

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St. Petersburg, Florida, United States

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Tampa, Florida, United States

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Honolulu, Hawaii, United States

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Boise, Idaho, United States

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Brownsburg, Indiana, United States

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Bowling Green, Kentucky, United States

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Elizabethtown, Kentucky, United States

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Louisville, Kentucky, United States

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Owensboro, Kentucky, United States

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Hagerstown, Maryland, United States

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Olive Branch, Mississippi, United States

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St Louis, Missouri, United States

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Missoula, Montana, United States

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Omaha, Nebraska, United States

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Brooklyn, New York, United States

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New York, New York, United States

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Charlotte, North Carolina, United States

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Greensboro, North Carolina, United States

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Hickory, North Carolina, United States

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Raleigh, North Carolina, United States

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Salisbury, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Portland, Oregon, United States

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Johnstown, Pennsylvania, United States

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Wyomissing, Pennsylvania, United States

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Charleston, South Carolina, United States

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Greer, South Carolina, United States

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Summerville, South Carolina, United States

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Bristol, Tennessee, United States

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Jackson, Tennessee, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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West Jordan, Utah, United States

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Spokane, Washington, United States

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Clarksburg, West Virginia, United States

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Newmarket, Ontario, Canada

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Sarnia, Ontario, Canada

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Toronto, Ontario, Canada

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Tbilisi, Georgia

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Related Publications (1)

• Poiley J, Steinberg AS, Choi YJ, Davis CS, Martin RL, McWherter CA, Boudes PF; Arhalofenate Flare Study Investigators. A Randomized, Double-Blind, Active- and Placebo-Controlled Efficacy and Safety Study of Arhalofenate for Reducing Flare in Patients With Gout. Arthritis Rheumatol. 2016 Aug;68(8):2027-34. doi: 10.1002/art.39684.

  PMID: 26989892 DERIVED

MeSH Terms

Conditions

Gout

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

Intervention Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: February 12, 2014
• First Posted: February 17, 2014
• Study Start: March 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: January 29, 2018

Record last verified: 2018-01

Locations

CA (3); GE (1); US (52)