Gout
Conditions
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.
Interventions
DRUGArhalofenate 600 mg
Arhalofenate 600 mg tablets once daily for 12 weeks
Allopurinol 300 mg tablets once daily for 12 weeks
Colchicine 0.6 mg over-encapsulated tablets once daily for 12 weeks
DRUGPlacebo
Placebo tablets once daily for 12 weeks
DRUGArhalofenate 800 mg
Arhalofenate 800 mg tablets once daily for 12 weeks
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Percent sUA reduction from baseline to Week 12 in the arhalofenate 800 mg group compared to the placebo group | 12 weeks |
| Time from baseline to onset of first flare for the arhalofenate 800 mg group compared to the allopurinol 300 mg group | 12 weeks |
| Time from baseline to onset of first flare for 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
| Measure | Time frame |
|---|---|
| Changes from baseline in fractional excretion of urate | 12 weeks |
| Changes from baseline in HbA1c and fasting TG in patients with HbA1c > 7.0% and TG > 150 mg/dL at baseline, respectively | 12 weeks |
| Adverse events (AE), and changes in vital signs and safety laboratory tests | 12 weeks |
| Proportion of patients experiencing at least one flare from baseline through Week 12 | 12 weeks |
| Flare-related study drug discontinuations | 12 weeks |
| Steady-state arhalofenate acid serum and urine concentrations | 12 weeks |
| Safety-related study drug discontinuations | 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 |
| Duration of flares | 12 weeks |
| Duration of flare treatment | 12 weeks |
| Flare composite score (summation of the daily maximum pain score on NRS during the duration of the flare) | 12 weeks |
| Proportion of patients experiencing flares who reached a sUA target < 6 mg/dL during treatment | 12 weeks |
| Evaluation of activity limitation associated with flare via HAQ-II | 12 weeks |
Countries
Canada, Georgia, United States
Outcome results
None listed