Clinical trial NCT02063997: Evaluate the Efficacy and Safety of Arhalofenate for Preventing Flares and Reducing Serum Uric Acid in Gout Patients
Official title: A Randomized, Double-Blind, Active and Placebo-Controlled Study to Evaluate the Efficacy and Safety of Arhalofenate for Preventing Flares and Reducing Serum Uric Acid in Gout Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gout
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-02-17
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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
* Must be able to swallow tablets/capsules
* Following training, must be willing and able to understand and complete an electronic diary

Exclusion Criteria:

* 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
* Current or expected chronic treatment with systemic corticosteroids (topical, ophthalmic, intra-articular or inhaled corticosteroid at a dose \< 1600 μg/day is permitted); per protocol a short course of oral corticosteroid may be used to treat flares occurring during the study
* History of intra-articular steroid injection to treat flare within four weeks of screening
* Known hypersensitivity or intolerance to allopurinol or colchicine
* Treatment with any other investigational therapy within 30 days or within five half lives, whichever is longer, prior to screening
* Patients who received arhalofenate in a previous trial
* Any other condition(s) that would compromise the safety of the patient, prevent compliance with the study protocol including ability to use an electronic diary, or compromise the quality of the clinical study, as judged by the Investigator and/or Medical Monitor

Primary outcomes:
measure: 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.
timeFrame: 12 weeks
Secondary outcomes:
measure: Percent sUA reduction from baseline to Week 12 in the arhalofenate 800 mg group compared to the placebo group
timeFrame: 12 weeks
measure: Percent sUA reduction from baseline to Week 12 in the arhalofenate 600 mg group compared to the placebo group
timeFrame: 12 weeks
measure: Proportion of patients with sUA < 6 mg/dL at Week 12 in the arhalofenate 800 mg group compared to the placebo group
timeFrame: 12 weeks
measure: The incidence of flares from baseline through Week 12 in the arhalofenate 600 mg group compared to the allopurinol 300 mg group
timeFrame: 12 weeks
measure: Proportion of patients with sUA < 6 mg/dL at Week 12 in the arhalofenate 600 mg group compared to placebo group
timeFrame: 12 weeks
measure: Time from baseline to onset of first flare for the arhalofenate 800 mg group compared to the allopurinol 300 mg group
timeFrame: 12 weeks
measure: Time from baseline to onset of first flare for the arhalofenate 600 mg group compared to the allopurinol 300 mg group
timeFrame: 12 weeks
Other outcomes:
measure: Proportion of patients experiencing at least one flare from baseline through Week 12
timeFrame: 12 weeks
measure: Proportion of patients experiencing two or more flares from baseline through Week 12
timeFrame: 12 weeks
measure: The incidence of flares from baseline through Week 4, from Week 5 through Week 8, and from Week 9 through Week 12
timeFrame: 12 weeks
measure: Duration of flares
timeFrame: 12 weeks
measure: Duration of flare treatment
timeFrame: 12 weeks
measure: Flare composite score (summation of the daily maximum pain score on NRS during the duration of the flare)
timeFrame: 12 weeks
measure: Proportion of patients experiencing flares who reached a sUA target < 6 mg/dL during treatment
timeFrame: 12 weeks
measure: Evaluation of activity limitation associated with flare via HAQ-II
timeFrame: 12 weeks
measure: Changes from baseline in fractional excretion of urate
timeFrame: 12 weeks
measure: Changes from baseline in HbA1c and fasting TG in patients with HbA1c > 7.0% and TG > 150 mg/dL at baseline, respectively
timeFrame: 12 weeks
measure: Adverse events (AE), and changes in vital signs and safety laboratory tests
timeFrame: 12 weeks
measure: Safety-related study drug discontinuations
timeFrame: 12 weeks
measure: Flare-related study drug discontinuations
timeFrame: 12 weeks
measure: Steady-state arhalofenate acid serum and urine concentrations
timeFrame: 12 weeks
Locations:
city: Birmingham
country: United States
state: Alabama
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: El Cajon
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Clearwater
country: United States
state: Florida
city: DeLand
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Honolulu
country: United States
state: Hawaii
city: Boise
country: United States
state: Idaho
city: Brownsburg
country: United States
state: Indiana
city: Bowling Green
country: United States
state: Kentucky
city: Elizabethtown
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Owensboro
country: United States
state: Kentucky
city: Hagerstown
country: United States
state: Maryland
city: Olive Branch
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: Missoula
country: United States
state: Montana
city: Omaha
country: United States
state: Nebraska
city: Brooklyn
country: United States
state: New York
city: New York
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Salisbury
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Johnstown
country: United States
state: Pennsylvania
city: Wyomissing
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Greer
country: United States
state: South Carolina
city: Summerville
country: United States
state: South Carolina
city: Bristol
country: United States
state: Tennessee
city: Jackson
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: West Jordan
country: United States
state: Utah
city: Spokane
country: United States
state: Washington
city: Clarksburg
country: United States
state: West Virginia
city: Newmarket
country: Canada
state: Ontario
city: Sarnia
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Tbilisi
country: Georgia
Study officials:
References:
citation: 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.