Clinical trial NCT01416402 (phase 2, status: completed)
Conditions: hyperuricemia, gout
ICD codes: E79.0, M10.9, M10.08, M10.00, M10.011, M10.012, M10.019, M10.021
Drugs: arhalofenate, febuxostat, colchicine
SMILES: CC(=O)NCCOC(=O)[C@H](OC1=CC=CC(=C1)C(F)(F)F)C1=CC=C(Cl)C=C1, CC(C)COC1=C(C=C(C=C1)C1=NC(C)=C(S1)C(O)=O)C#N, COC1=CC2=C(C(OC)=C1OC)C1=CC=C(OC)C(=O)C=C1C(CC2)NC(C)=O
Eligibility criteria:

        Inclusion Criteria:

          1. Known gout patient (per criteria of the American Rheumatism Association for the
             classification of the acute arthritis of primary gout in Appendix 3) with a serum uric
             acid value of at least 8.0 mg/dL at Screening Visit. Patients on allopurinol must
             agree to discontinue their existing therapy at Visit 1 through the entire duration of
             the study and must have a sUA value of at least 8.0 mg/dL after a minimum 2 week
             wash-out at Visit 2.

          2. Male or female, 18-75 years of age at Screening Visit

          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 6 months and serum FSH ≥ 40 mIU/mL) 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 report of 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
             condom or the partner must use a medically acceptable method of contraception for the
             entire duration of the study.

          6. Estimated CrCl ≥ 50 mL/min as calculated by the by Cockcroft-Gault method

          7. Serum creatinine value must be ≤ 1.3 mg/dL in females and ≤ 1.4 mg/dL in males

          8. Patients must have liver function tests (LFTs) ≤ 1.5X ULN for AST, ALT and
             T-bilirubin, ≤ 2X ULN for ALP, ≤ 3X ULN for GGT; CK ≤ 3X ULN

          9. All other clinical laboratory parameters must be within normal limits or considered
             not clinically significant

         10. Electrocardiogram (ECG) must be normal, or if abnormal, considered not clinically
             significant

         11. Patients must have a systolic blood pressure ≤ 160 mm Hg and a diastolic blood
             pressure ≤ 95 mm Hg; known hypertensive patients controlled with medication other than
             diuretics (BP reading as above) may be included

         12. Patients must agree to remain in-clinic for 37 days consecutively and agree to follow
             the study procedures as described in the protocol

        Exclusion Criteria:

          1. Treatment with any ULT other than allopurinol (e.g., probenecid, benzbromarone,
             febuxostat, or pegloticase) within two weeks 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 the human immunodeficiency virus (HIV) or history of viral
             hepatitis type B or C

          6. History of illicit drug or alcohol abuse within one year of Screening Visit

          7. History of significant pulmonary disease, upper gastrointestinal (GI) bleeding,
             documented peptic ulcer disease (unless known H. pylori infection treated successfully
             without recurrence), or nephrotic syndrome within three years of Screening Visit

          8. History of stroke, TIA, acute myocardial infarction (MI), congestive heart failure
             (CHF) (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 5
             years of screening

          9. Malignancy within five years of Screening Visit (except successfully treated basal
             cell carcinoma)

         10. Body mass index (BMI) > 42 kg/m2

         11. Current or expected requirement for anticoagulant therapy [except for low-dose (≤ 325
             mg/day) aspirin and/or Plavix® 75 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, theophyline, desipramine, sulphonylurea, thiazolidinedione,
             diuretics, atypical antipsychotic agents, or phenytoin

         14. Chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs use to treat
             acute gout flares is 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 gout flares

         16. Known hypersensitivity to colchicine or febuxostat

         17. Treatment with any other investigational therapy within the 30 days prior to the
             Screening Visit, or patients who received at least one dose of blinded study
             medication while enrolled in any previous arhalofenate 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