Methods for Treating Gout in Patients Subpopulations

1 . A method of lowering serum uric acid level in a subject with impaired renal function, comprising administering to the subject a compound of Formula (I)

wherein R is selected from the group consisting of hydroxy, lower aralkoxy, di-lower alkylamino-lower alkoxy, lower alkanamido-lower alkoxy, benzamido-lower alkoxy, ureido-lower alkoxy, N′-lower alkyl-ureido-lower alkoxy, carbamoyl-lower alkoxy, halophenoxy-substituted lower alkoxy, carbamoyl-substituted phenoxy, carbonyl-lower alkylamino, N,N-di-lower alkylamino-lower alkylamino, halo-substituted lower alkylamino, hydroxyl-substituted lower alkylamino, lower alkanolyloxy-substituted lower alkylamino, ureido, and lower alkoxycarbonylamino; and each X is independently a halogen; or a pharmaceutically acceptable salt thereof.

2 . The method of claim 1 , wherein the compound or a pharmaceutically acceptable salt thereof is (−)-halofenate or (−)-halofenic acid, or a pharmaceutically acceptable salt thereof.

3 . The method of claim 1 , wherein the compound (−)-halofenate.

4 . A method of treating a subject having a condition associated with an elevated serum uric acid level and with impaired renal function, comprising administering to the subject a compound of Formula (I)

wherein R is selected from the group consisting of hydroxy, lower aralkoxy, di-lower alkylamino-lower alkoxy, lower alkanamido-lower alkoxy, benzamido-lower alkoxy, ureido-lower alkoxy, N′-lower alkyl-ureido-lower alkoxy, carbamoyl-lower alkoxy, halophenoxy-substituted lower alkoxy, carbamoyl-substituted phenoxy, carbonyl-lower alkylamino, N,N-di-lower alkylamino-lower alkylamino, halo-substituted lower alkylamino, hydroxyl-substituted lower alkylamino, lower alkanolyloxy-substituted lower alkylamino, ureido, and lower alkoxycarbonylamino; and each X is independently a halogen; or a pharmaceutically acceptable salt thereof.

5 . The method of claim 4 , wherein the compound or a pharmaceutically acceptable salt thereof is (−)-halofenate or (−)-halofenic acid, or a pharmaceutically acceptable salt thereof.

6 . The method of claim 4 , wherein the compound is (−)-halofenate.

7 . The method of claim 4 , wherein the condition associated with an elevated serum uric acid level is gout.

8 . The method of claim 5 , wherein the condition is acute gout, chronic gout, moderate gout, refractory gout or severe gout.

9 . A method for the treatment of hyperuricemia in a subject with gout comprising administering to the subject in need thereof a compound of Formula (I) of claim 1 or a pharmaceutically acceptable salt thereof, wherein the subject has impaired renal function.

10 . The method of claim 9 , wherein the compound of Formula (I) of claim 1 or a pharmaceutically acceptable salt thereof is a compound of Formula (II)

wherein R 2 is a selected from the group consisting of phenyl-lower alkyl, lower alkanamido-lower alkyl, and benzamido-lower alkyl, and each X is independently a halogen; or a pharmaceutically acceptable salt thereof.

11 . The method of claim 9 , wherein the compound or a pharmaceutically acceptable salt thereof is (−)-halofenate or (−)-halofenic acid, or a pharmaceutically acceptable salt thereof.

12 . The method of claim 9 , wherein the compound is (−)-halofenate.

13 . The method of claim 9 , wherein the impaired renal function is chronic kidney disease.

14 . The method of claim 13 , wherein the chronic kidney disease is mild or moderate.

15 . The method of claim 13 , wherein the chronic kidney disease is severe.

16 . The method of claim 9 , wherein the compound is administered at a dose that is independent of the stage of chronic kidney disease.

17 . The method of claim 9 , wherein the administration of the compound results in no clinically significant adverse effect on renal function.

18 . The method of claim 9 , wherein the administration of the compound results in a lowering of HbA1c, blood glucose, or fasting plasma glucose levels.

19 . The method of claim 9 , wherein the administration of the compound results in a lowering of triglyceride levels.

20 . The method of claim 9 , wherein the compound is (−)-halofenate and the compound is administered at from about 100 mg to about 1000 mg per day.

21 . The method of claim 9 , wherein the subject is undergoing aspirin or a diuretic therapy.

22 . The method of claim 7 , further comprising the administration of a second urate-lowering agent selected from the group consisting of a xanthine oxidase inhibitor, an inhibitor of uric acid production, a uricosuric agent and a uricase.

23 . The method of claim 7 , wherein the second urate-lowering agent is selected from the group consisting of allopurinol, febuxostat, ulodesine, forodesine, oxypurinol, tisopurine, inositol, phytic acid, myo-inositiol, kaempferol, myricetin, quercetin, probenecid, 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)acetic acid, potassium 4-(2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)acetamido)-3-chlorobenzoate, RDEA684, benzbromarone, sulfinpyrazone, amlodipine, atorvastatin, fenofibrate, levotofisopam, guaifenesin, losartan, adrenocorticotropic hormone and cortisone.

24 . The method of claim 23 , wherein second urate-lowering agent is febuxostat.