Methods for treating disorders or diseases associated with hyperlipidemia and hypercholesterolemia while minimizing side-effects

• US 9,265,758 B2
• Filed: 11/08/2013
• Issued: 02/23/2016
• Est. Priority Date: 03/05/2004
• Status: Active Grant

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Rader, Daniel J.
• Primary Examiner(s): Weddington, Kevin E
• Application Number:
  US14/075,483
• Publication Number:
  US 20140303209A1
• Time in Patent Office: 837 Days
• Field of Search: 514/321, 514/325, 514/252.03, 514/255.03
• US Class Current: 1/1
• CPC Class Codes: A61K 31/21 Esters, e.g. nitroglycerine, selenocyanates
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

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.

Claims

1. 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 the dose levels are from about 2 to about 13 mg/day, from about 5 to about 30 mg/day, and from about 10 to about 50 mg/day;

and wherein the MTP inhibitor is represented by;

2. The method of claim 1 wherein the disorder is severe hypercholesterolemia.

3. The method of claim 1 wherein one or more of Total Cholesterol, LDL, fasting triglycerides (TG), VLDL, lipoprotein (a) (Lp(a)), and apolipoproteins A-I, A-II, B, and E are reduced by at least 15%, compared to control levels.

4. The method of claim 1 wherein one or more of Total Cholesterol, LDL, fasting triglycerides (TG), VLDL, lipoprotein (a) (Lp(a)), and apolipoproteins A-I, A-II, B, and E are reduced by at least 25%, compared to control levels.

5. The method of claim 1 wherein the MTP inhibitor is administered orally.

6. The method of claim 1 wherein said increasing dose levels further comprise a fourth dose level.

7. 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 up to a maximum dose level, wherein a first starting dose level is from about 2 to about 13 mg/day, a second dose level is from about 5 to about 30 mg/day, and a third dose level is from about 10 to about 50 mg/day;

and wherein the MTP inhibitor is represented by;

8. The method of claim 7, wherein the administering increasing dose levels further comprises a fourth dose level of about 20 to about 60 mg/day and a maximum dose level of about 30 to about 75 mg/day.

9. 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 a first dose level is from about 2 to about 13 mg/day, a second dose level is from about 5 to about 30 mg/day, and a third dose level is from about 10 to about 50 mg/day;

and wherein the MTP inhibitor is represented by;

10. The method of claim 9, wherein the administering increasing dose levels further comprises a fourth dose level of about 20 to about 60 mg/day and a maximum dose level of about 30 to about 75 mg/day.