Claims for Patent: 11,998,542

Summary for Patent: 11,998,542

Title:	Compositions and methods for reducing major adverse cardiovascular events
Abstract:	The present application relates to compositions, kits, uses, systems and methods of using naltrexone and bupropion, or pharmaceutically acceptable salts thereof, for reducing the risk of adverse cardiovascular outcomes or events, including Major Adverse Cardiovascular Events (MACE) in subjects, preferably those at increased risk of adverse cardiovascular outcomes or MACE, that may be overweight or obese. The present application also relates to compositions, kits, uses, systems and methods of using naltrexone and bupropion or pharmaceutically acceptable alts thereof for treatment of overweight or obesity in subjects, preferably at increased risk of adverse cardiovasular outcomes or MACE, wherein the treatment reduce, the risk of MACE.
Inventor(s):	Preston Klassen, Kristin Taylor
Assignee:	Nalpropion Pharmaceuticals LLC
Application Number:	US17/099,316
Patent Claims:	1. A method of administering naltrexone and bupropion to a subject having an increased risk of a major adverse cardiovascular event (MACE), the method comprising: administering to the subject a daily dose of 4-50 mg of naltrexone, or a pharmaceutically acceptable salt thereof, and 50-400 mg of bupropion, or a pharmaceutically acceptable salt thereof, for a treatment period of at least 1 week, wherein the subject is a smoker. 2. The method of claim 1, wherein the smoker is a smoker at the beginning of the treatment period. 3. The method of claim 1, wherein the subject has a history of cardiovascular disease. 4. The method of claim 3, 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. 5. The method of claim 1, wherein the MACE is selected from the group consisting of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. 6. The method of claim 1, wherein the treatment period is at least 12 weeks. 7. The method of claim 1, wherein the subject is administered: about 8 mg of naltrexone or a pharmaceutically acceptable salt thereof and about 90 mg of bupropion or a pharmaceutically acceptable salt thereof daily for a first week of treatment; about 16 mg of naltrexone or a pharmaceutically acceptable salt thereof and about 180 mg of bupropion or a pharmaceutically acceptable salt thereof daily for a second week of treatment; about 24 mg of naltrexone or a pharmaceutically acceptable salt thereof and about 270 mg of bupropion or a pharmaceutically acceptable salt thereof daily for a third week of treatment; and about 32 mg of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof for the fourth and any subsequent weeks of treatment. 8. The method of claim 1, wherein the naltrexone and bupropion, or pharmaceutically acceptable salts thereof, are administered in a sustained release formulation. 9. The method of claim 1, wherein the naltrexone and bupropion, or pharmaceutically acceptable salts thereof, are administered in a single oral unit dosage form. 10. The method of claim 1, wherein the naltrexone salt comprises naltrexone hydrochloride and the bupropion salt comprises bupropion hydrochloride. 11. A method of reducing risk of a major adverse cardiovascular event (MACE) in a smoker, the method comprising: administering to the smoker a daily dose of 4-50 mg of naltrexone, or a pharmaceutically acceptable salt thereof, and 50-400 mg of bupropion, or a pharmaceutically acceptable salt thereof, for a treatment period of at least 1 week, wherein said administering reduces the risk of MACE compared to a smoker not receiving the daily dose of naltrexone, or a pharmaceutically acceptable salt thereof, and bupropion, or a pharmaceutically acceptable salt thereof. 12. The method of claim 11, wherein the smoker is a smoker at the beginning of the treatment period. 13. The method of claim 11, wherein the subject has a history of cardiovascular disease. 14. The method of claim 13, 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. 15. The method of claim 13, wherein the MACE is selected from the group consisting of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. 16. The method of claim 13, wherein the treatment period is at least 12 weeks. 17. The method of claim 13, wherein the subject is administered: about 8 mg of naltrexone or a pharmaceutically acceptable salt thereof and about 90 mg of bupropion or a pharmaceutically acceptable salt thereof daily for a first week of treatment; about 16 mg of naltrexone or a pharmaceutically acceptable salt thereof and about 180 mg of bupropion or a pharmaceutically acceptable salt thereof daily for a second week of treatment; about 24 mg of naltrexone or a pharmaceutically acceptable salt thereof and about 270 mg of bupropion or a pharmaceutically acceptable salt thereof daily for a third week of treatment; and about 32 mg of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof for the fourth and any subsequent weeks of treatment. 18. The method of claim 13, wherein the naltrexone and bupropion, or pharmaceutically acceptable salts thereof, are administered in a sustained release formulation. 19. The method of claim 13, wherein the naltrexone and bupropion, or pharmaceutically acceptable salts thereof, are administered in a single oral unit dosage form. 20. The method of claim 13, wherein the naltrexone salt comprises naltrexone hydrochloride and the bupropion salt comprises bupropion hydrochloride.