Compositions and methods for weight loss in at risk patient populations

• US 10,231,964 B2
• Filed: 10/05/2017
• Issued: 03/19/2019
• Est. Priority Date: 12/06/2013
• Status: Active Grant

• Current Assignee: Nalpropion Pharmaceuticals LLC
• Original Assignee: Nalpropion Pharmaceuticals, Inc. (Currax Holdings USA, LLC)
• Inventors: Klassen, Preston, Taylor, Kristin
• Primary Examiner(s): Rao, Savitha M
• Application Number:
  US15/725,830
• Publication Number:
  US 20180243288A1
• Time in Patent Office: 530 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• 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
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The present disclosure relates to compositions, kits, uses, systems and methods related to naltrexone plus bupropion for treating an overweight or obese subject at increased risk of adverse cardiovascular outcomes. Preferably, the subject has had type-two diabetes for a period of less than 6 years or is a current smoker, optionally that does not have type-two diabetes.

Claims

1. A method of treating overweight or obesity in a subject having an increased risk of adverse cardiovascular outcomes, the method comprising:

treating the subject for overweight or obesity by administering to the subject a daily dose of 32 mg of sustained release naltrexone, or a pharmaceutically acceptable salt thereof, and 360 mg bupropion, or a pharmaceutically acceptable salt thereof, for a period of at least 12 weeks.

2. The method of claim 1, wherein the subject

is a current smoker that does not have type-two diabetes.

3. The method of claim 1, wherein the subject was administered:

about 8 mg of said sustained release naltrexone or a pharmaceutically acceptable salt thereof and about 90 mg of said sustained release bupropion or a pharmaceutically acceptable salt thereof daily for a first week of treatment;

about 16 mg of said sustained release naltrexone or a pharmaceutically acceptable salt thereof and about 180 mg of said sustained release bupropion or a pharmaceutically acceptable salt thereof daily for a second week of treatment;

about 24 mg of said sustained release naltrexone or a pharmaceutically acceptable salt thereof and about 270 mg of said sustained release bupropion or a pharmaceutically acceptable salt thereof daily for a third week of treatment; and

about 32 mg of said sustained release naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of said sustained release bupropion or a pharmaceutically acceptable salt thereof daily for a fourth week of treatment and any subsequent weeks of treatment.

4. The method of claim 1, wherein the period of treatment is at least 20 weeks.

5. The method of claim 2, wherein the subject was administered:

about 8 mg of said sustained release naltrexone or a pharmaceutically acceptable salt thereof and about 90 mg of said sustained release bupropion or a pharmaceutically acceptable salt thereof daily for a first week of treatment;

about 16 mg of said sustained release naltrexone or a pharmaceutically acceptable salt thereof and about 180 mg of said sustained release bupropion or a pharmaceutically acceptable salt thereof daily for a second week of treatment;

about 24 mg of said sustained release naltrexone or a pharmaceutically acceptable salt thereof and about 270 mg of said sustained release bupropion or a pharmaceutically acceptable salt thereof daily for a third week of treatment; and

about 32 mg of said sustained release naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of said sustained release bupropion or a pharmaceutically acceptable salt thereof daily for a fourth week of treatment and any subsequent weeks of treatment.

6. The method of claim 2, wherein the period of treatment is at least 20 weeks.

7. The method of claim 1, wherein the subject has type-two diabetes.

8. The method of claim 7, wherein the subject has had type-two diabetes for less than 6 years.

9. The method of claim 1, wherein the subject is a current smoker.

10. The method of claim 1, wherein the subject has a history of cardiovascular disease.

11. The method of claim 10, wherein the subject has one or more of:

a history of documented myocardial infarction more than 3 months prior to treatment;

a history of coronary, carotid or peripheral revascularization;

angina with ischemic changes,

ECG changes on a graded exercise test;

positive cardiac imaging study;

ankle brachial index less than 0.9 within 2 years prior to treatment;

or

greater than 50% stenosis of a coronary, carotid, or lower extremity artery within 2 years prior to treatment.

12. The method of claim 1, wherein administering the sustained release naltrexone or a pharmaceutically acceptable salt thereof and sustained release bupropion or a pharmaceutically acceptable salt thereof decreases the subject'"'"'s risk of a major adverse cardiovascular outcome.

13. The method of claim 7, wherein administering the sustained release naltrexone or a pharmaceutically acceptable salt thereof and sustained release bupropion or a pharmaceutically acceptable salt thereof decreases the subject'"'"'s risk of a major adverse cardiovascular outcome.

14. The method of claim 8, wherein administering the sustained release naltrexone or a pharmaceutically acceptable salt thereof and sustained release bupropion or a pharmaceutically acceptable salt thereof decreases the subject'"'"'s risk of a major adverse cardiovascular outcome.

15. The method of claim 9, wherein administering the sustained release naltrexone or a pharmaceutically acceptable salt thereof and sustained release bupropion or a pharmaceutically acceptable salt thereof decreases the subject'"'"'s risk of a major adverse cardiovascular outcome.

16. The method of claim 1, wherein the adverse cardiovascular outcome is selected from the group consisting of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

17. The method of claim 12, wherein the adverse cardiovascular outcome is selected from the group consisting of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

18. The method of claim 13, wherein the adverse cardiovascular outcome is selected from the group consisting of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

19. The method of claim 14, wherein the adverse cardiovascular outcome is selected from the group consisting of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

20. The method of claim 15, wherein the adverse cardiovascular outcome is selected from the group consisting of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.