EP-4739305-A1 - BUDIODARONE FOR CARDIOVERSION

Abstract

Disclosed are cardioversion methods for patients with either paroxysmal or persistent AFib which methods use budiodarone or a pharmaceutical composition comprising budiodarone.

Inventors

• DRUZGALA, PASCAL
• MILNER, PETER

Assignees

• Xyra, LLC

Dates

Publication Date

20260513

Application Date

20240702

Claims (20)

1. 1. A method for cardioverting a patient with paroxysmal or persistent AFib suffering from an extended episode of AFib and deemed suitable for cardioversion, said method comprising: a) administering budiodarone or a pharmaceutically acceptable salt thereof to said patient in an amount sufficient to effect cardioversion of said AFib back to sinus rhythm, wherein the patient has been confirmed as having paroxysmal or persistent AFib; and b) monitoring said patient subsequent to said administration to confirm that the patient is responsive to cardioversion.
2. 2. A method for cardioverting a patient with paroxysmal or persistent AFib suffering from an extended episode of AFib, said method comprising: a) administering a sufficient amount of budiodarone or a salt thereof to said patient to achieve a plasma concentration of budiodarone a salt thereof at least about 13 ng/ mL for a period of time to cardiovert said patient back to sinus rhythm, wherein the patient has been confirmed as having paroxysmal or persistent AFib and deemed suitable for cardioversion; and b) monitoring said patient subsequent to said administration to confirm that the patient is responsive to cardioversion.
3. 3. The method of claim 1, wherein the amount of budiodarone or a salt thereof administered to said patient is sufficient to provide for a plasma concentration of from about 13 ng/mL to about 350 ng/mL in said patient, provided that the plasma concentration of budiodarone remains greater than 13 ng/mL for at least 6 hours post-administration.
4. 4. The method of claim 3, wherein the amount of budiodarone or a salt thereof administered to said patient is sufficient to provide a plasma concentration of budiodarone or a salt thereof in said patient to about 50 ng/mL to about 350 ng/mL for at least about 5 hours.
5. 5. The method of claim 4, wherein the amount of budiodarone or a salt thereof administered to said patient is sufficient to provide for a plasma concentration of budiodarone or a salt thereof of about 50 ng/mL to about 350 ng/mL for at least about 6 hours.
6. 6. The method of claim 1, wherein said budiodarone or a salt thereof administration is oral, sublingual, intravenous, rectal, or an aerosol.
7. 7. The method of claim 6, wherein budiodarone or salt thereof is administered orally using capsules, pills, or tablets.
8. 8. The method of claim 7, wherein budiodarone or a salt thereof is administered to said patient in a single dose of from about 400 mg to about 2,000 mg.
9. 9. The method of claim 8, wherein budiodarone or a salt thereof is administered to said patient in a single dose of from about 800 mg to about 1,200 mg.
10. 10. The method of claim 8, wherein budiodarone or a salt thereof is administered as a single dose of about 1,000 mg.
11. 11. The method of claim 8, wherein budiodarone or a salt thereof is administered as a single dose of about 1,200 mg.
12. 12. The method of claim 1, which further comprises administering a blood thinner with budiodarone or a salt thereof, wherein the blood thinner is dabigatran, edoxaban, apixaban, or rivaroxaban.
13. 13. The method of any one of claims 1, wherein cardioversion is accomplished in about 90 minutes or less from budiodarone or a salt thereof administration.
14. 14. The method of claim 13, wherein cardioversion is accomplished in about 60 minutes or less from budiodarone or a salt thereof administration.
15. 15. The method of claim 13, wherein cardioversion is accomplished in about 45 minutes or less from budiodarone or a salt thereof administration.
16. 16. The method of claim 13, wherein cardioversion is accomplished in about 30 minutes or less from budiodarone or salt thereof administration.
17. 17. The method of claim 1, wherein said patient is fed about 1 hour or less before administration of budiodarone or a salt thereof.
18. 18. The method of claim 1, wherein said budiodarone or a salt thereof is budiodarone tartrate.
19. 19. A kit of parts comprising a single dose of budiodarone or salt thereof effective in cardioverting a patient and instructions for post-administration monitoring of the patient.
20. 20. A method comprising of cardioverting a patient back to normal sinus rhythm comprising administering a dose of budiodarone or a salt thereof to the patient in need of cardioversion determined to have either paroxysmal or persistent AFib, wherein the dose is sufficient to produce an effective plasma level of >50 ng/ml in said patient within 60 min of administering the dose, and maintaining a plasma level in said patient of >50 ng/ml for up to 6 hours thereby cardioverting a single sustained long episode of PAF, or a storm of long PAF episodes, or a persistent AFib episode back to normal sinus rhythm in said patient.

Description

BUDIODARONE FOR CARDIOVERSION Background Cross-Reference [0001] This application claims the benefit of U.S. Non-Provisional Application No. 18/351,261, filed July 12, 2023, which claims the benefit of U.S. Provisional Application No. 63/525,014, filed July 5, 2023, each of which is incorporated by reference herein in its entirety. Field [0002] This disclosure provides for methods to cardiovert patients with either paroxysmal or persistent atrial fibrillation (AFib) back to sinus rhythm which methods use a pharmaceutical composition comprising budiodarone. Related Applications [0003] This application claims benefit of U.S. provisional application 63/525,014 filed on July 5, 2023. The entire contents of which is incorporated by reference. State of the Art [0004] Patients suffering from paroxysmal or persistent AFib experiencing a prolonged episode of AFib are at elevated risk of a stroke and/or congestive heart failure. These risks increase as the duration of the episode extends. Patients with symptomatic paroxysmal or persistent AFib are significantly more likely to recognize their condition whereas asymptomatic patients on a heart rhythm monitor that provides an alarm-based warning of prolonged AFib will become aware of their condition once the alarm has been activated. In either case, many such patients presenting themselves at a hospital emergency room or are in a critical care unit with such an extended episode of AFib are treated by having a cardioversion procedure typically by stopping the heart and restarting it in order to restore sinus rhythm. Currently, there are from about 70,000 to perhaps as high as 100,000 or more cardioversions done each year with the number increasing as the population ages. These numbers represent a fraction of patients who present themselves in emergency rooms with AFib. One reference suggested that about 25% of patients presenting at the emergency room with AFib were treated with cardioversion. Gulizia et al., Europace. 2019;21(2): 230-238. This suggests that some of the non-treated patients were contra-indicated for this procedure due to co-morbidities and some had their sinus rhythm restored without cardioversion. [0005] The method of choice for cardioversion is electrical cardioversion, which relies upon stopping and restarting the heart to restore sinus rhythm. However, this procedure comes with several shortcomings. From the patient's perspective, there is a risk of dying during or within a few months after this procedure due to, for example, the release of blood clots from the heart during electrical cardioversion. From the clinician’s perspective, electrical cardioversions require at least one or more nurses, an anesthesiologist, a cardiologist, the use of an anti -coagulant, and the like all at a significant cost to the health care system. From a cost perspective, cardioversion can cost thousands of dollars which, given the number of cardioversions conducted annually, imposes a significant cost burden on the healthcare system, particularly when the costs for treating patients who have a blood clot that releases during or shortly after the procedure or are included. Summary [0006] Disclosed are methods to cardiovert a patient with an extended episode of paroxysmal or persistent AFib that utilizes a single high dose of budiodarone or a pharmaceutically acceptable salt thereof to effect cardioversion of the AFib sinus rhythm in said patient. The single high dose of budiodarone or a pharmaceutically acceptable salt thereof is preferably administered orally but other routes of administration are contemplated herein including intravenous, rectal, and pulmonary administration. The patient undergoing cardioversion is first deemed suitable for the procedure. [0007] In one embodiment, there is provided a method for cardioverting a patient with paroxysmal or persistent AFib suffering from an extended episode of AFib, said method comprising: a) evaluating the patient to confirm that the patient has paroxysmal or persistent AFib and is suitable for cardioversion; b) administering budiodarone or a pharmaceutically acceptable salt thereof to said patient in an amount sufficient to effect cardioversion of said AFib back to sinus rhythm in said patient; and c) monitoring said patient subsequent to said administration to confirm that the patient is responsive to cardioversion. [0008] In another embodiment, a method is provided for cardioverting a patient with paroxysmal or persistent AFib suffering from an extended episode of AFib and deemed suitable for cardioversion, said method comprising: a) administering of budiodarone or a pharmaceutically acceptable salt thereof to said patient in an amount sufficient to effect cardioversion of said AFib back to sinus rhythm, wherein the patient has been confirmed as having paroxysmal or persistent AFib as well as being deemed suitable for cardioversion; and b) monitoring said patient subsequent to said administration to confirm that the