Methods for the treatment of nonalcoholic fatty liver disease and/or lipodystrophy
The present invention relates to methods for treating a disease associated with insulin resistance selected from a nonalcoholic fatty liver disease (NAFLD) and its sequelae, a lipodystrophic syndrome or a combination thereof with the selective PPARγ agonist, INT131 and optionally vitamin E or compositions thereof. NAFLDs that may be treated with methods and compositions of the present invention include, but are not limited to, simple nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH). Lipodystrophic syndromes that may be treated with the methods and compositions of the present invention include, but are not limited to, generalized lipodystrophy including congenital generalized lipodystrophy and acquired generalized lipodystrophy and/or partial lipodystrophy, including congenital partial lipodystrophy and acquired partial lipodystrophy, all of which may or may not include hyperlipidemia and/or hyperglycemia and may or may not include NAFLD.
1. A method of treating nonalcoholic steatohepatitis (NASH) comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I):
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 further comprising administering to a subject in need thereof an amount of vitamin E.
3. The method of claim 2 wherein the compound of formula I and vitamin E are administered concomitantly, simultaneously or consecutively.
4. The method of claim 2 wherein the amount of the compound of formula I is from about 0.1 to about 10.0 milligrams (“mg”) per day and wherein the amount of vitamin E is from about 1 to about 10,000 international units (“IU”) per day.
5. The method of claim 4 wherein the amount of the compound of formula I is from about 1 mg to about 2 mg and the amount of vitamin E is from about 400 to about 1,000 IU per day.
6. The method of claim 5 wherein the amount of the compound of formula I is about 1 or about 2 mg per day and the amount of vitamin E is about 400, about 800 or about 1,000 IU per day.
7. The method of claim 1 wherein the subject is a human.
8. The method of claim 1 wherein the NASH is NASH with attendant liver fibrosis.
9. The method of claim 1 wherein the NASH is NASH with attendant liver cirrhosis.
10. The method of claim 1 wherein the amount of formula (I) is from about 0.1 to about 10.0 mg per day.
11. The method of claim 10 wherein the amount of formula (I) is about 1 mg per day.
12. The method of claim 10 wherein the amount of formula (I) is about 2 mg per day.
13. The method of claim 1 wherein the method provides an NAFLD activity score (NAS) of 7 or less.
14. The method of claim 13 wherein the NAS is 5 or less.
15. The method of claim 13 wherein the NAS is 3 or less.
16. The method of claim 4 wherein the amount of the compound of formula I is from about 1 to about 5 mg per day and wherein the amount of vitamin E is from about 1 to about 10,000 IU per day.
17. The method of claim 4 wherein the amount of the compound of formula I is from about 1 mg to about 5 mg and the amount of vitamin E is from about 400 to about 1,000 IU per day.
18. The method of claim 10 wherein the amount of formula (I) is from about 1 to about 5 mg per day.