Claims for Patent: 9,433,617

Summary for Patent: 9,433,617

Title:	Methods for treating disorders or diseases associated with hyperlipidemia and hypercholesterolemia while minimizing side-effects
Abstract:	The present invention provides methods and compositions for treating hyperlipidemia and/or hypercholesterolemia comprising administering to the subject an effective amount of an MTP inhibitor to inhibit hyperlipidemia and/or hypercholesterolemia in said subject, wherein said administration comprises an escalating series of doses of the MTP inhibitor. In some embodiments the method comprises administering at least three step-wise, increasing dosages of the MTP inhibitor to the subject. In some embodiments, the method further comprises the administration of one or more other lipid modifying compounds.
Inventor(s):	Rader; Daniel J. (Philadelphia, PA)
Assignee:	The Trustees of the University of Pennsylvania (Philadelphia, PA)
Application Number:	15/155,647
Patent Claims:	1. A method of treating a subject suffering from hyperlipidemia or hypercholesterolemia, the method comprising orally administering to the subject an effective amount of an MTP inhibitor, wherein said administration comprises three step-wise, increasing dose levels of the MTP inhibitor, wherein each dose level is 50% of the immediately following dose level, wherein the third dose level is about 0.2 to about 0.59 mg/kg/day, and wherein the MTP inhibitor is N-(2,2,2-trifluoroethyl)-9-[4-[4-[[[4'-(trifluoromethyl)[1,1'-biphenyl]-2- -yl] carbonyl] amino]-1-piperidinyl]butyl]-9H-fluorene-9-carboxamide, methanesulfonate; and wherein each dose level is administered about 1 to about 12 weeks. 2. The method of claim 1, wherein the subject suffering from hyperlipidemia or hypercholesterolemia has homozygous familial hypercholesterolemia. 3. The method of claim 1, where each dose level is administered about 7 to about 35 days. 4. The method of claim 1, wherein the first dose level is administered for about 2 weeks and the second and third dose levels are each administered for about 4 weeks. 5. The method of claim 1, wherein administration further comprises a fourth dose level, wherein the third dose level is 50% of the fourth dose level. 6. The method of claim 5, upon administration, the LDL-cholesterol of the subject is reduced by at least 25% compared to pre-treatment levels. 7. The method of claim 1, wherein upon administration the subject has reduced symptoms of steatorrhea and/or hepatic fat as compared to a subject administered a starting dose of 25 mg/day of the MTP inhibitor. 8. A method of treating a subject suffering from hyperlipidemia or hypercholesterolemia the method comprising administering to the subject an effective amount of an MTP inhibitor, wherein said administration comprises at least three step-wise, increasing dose levels of the MTP inhibitor, wherein each dose level is 50% of the immediately following dose level, wherein the second dose level is about 0.06 mg/kg/day to about 0.19 mg/kg/day, wherein the MTP inhibitor is N-(2,2,2-trifluoroethyl)-9-[4-[4-[[[4'-(trifluoromethyl)[l,r-biphenyl]-2-- yl] carbonyl] amino]-l-piperidinyl]butyl]-9H-fluorene-9-carboxamide, methanesulfonate, and wherein each dose level is administered about 1 to about 12 weeks. 9. The method of claim 8, wherein the subject suffering from hyperlipidemia or hypercholesterolemia has homozygous familial hypercholesterolemia. 10. The method of claim 8, where each dose level is administered about 7 to about 35 days. 11. The method of claim 8, wherein the first dose level is administered for about 2 weeks and the second and third dose levels are each administered for about 4 weeks. 12. The method of claim 8, wherein said increasing dose levels further comprise a fourth dose level, wherein the third dose level is 50% of the fourth dose level. 13. The method of claim 12, upon administration, the LDL-cholesterol of the subject is reduced by at least 25% compared to pre-treatment levels. 14. The method of claim 8, wherein upon administration the subject has reduced symptoms of steatorrhea and/or hepatic fat as compared to a subject administered a starting dose of 25 mg/day of the MTP inhibitor. 15. A method of treating a subject suffering from hyperlipidemia or hypercholesterolemia, the method comprising administering to the subject an effective amount of an MTP inhibitor, wherein said administration comprises three step-wise, increasing dose levels of the MTP inhibitor, wherein each dose level is no more than 50% of the immediately following dose level, and wherein the first dose level is about 0.02 to about 0.059 mg/kg/day, the second dose level is about 0.06 mg/kg/day to about 0.19 mg/kg/day, and the third dose level is about 0.2 to about 0.59 mg/kg/day; wherein the MTP inhibitor is N-(2,2,2-trifluoroethyl)-9-[4-[4-[[[4'-(trifluoromethyl)[l,r-biphenyl]-2-- yl] carbonyl] amino]-l-piperidinyl]butyl]-9H-fluorene-9-carboxamide, methanesulfonate; and wherein each dose level is administered about 1 to about 12 weeks. 16. The method of claim 15, wherein the subject suffering from hyperlipidemia or hypercholesterolemia has homozygous familial hypercholesterolemia. 17. The method of claim 15, where each dose level is administered about 7 to about 35 days. 18. The method of claim 15, wherein said increasing dose levels further comprise a fourth dose level, wherein the fourth dose level is about 0.6 to about 2.0 mg/kg/day. 19. The method of claim 18, upon administration, the LDL-cholesterol of the subject is reduced by at least 25% compared to pre-treatment levels. 20. The method of claim 15, wherein upon administration the subject has reduced symptoms of steatorrhea and/or hepatic fat as compared to a subject administered a starting dose of 25 mg/day of the MTP inhibitor.