Claims for Patent: 12,257,224

Summary for Patent: 12,257,224

Title:	Methods of administration for highly water-soluble salts of a short acting phenylalkylamine calcium channel blocker
Abstract:	The present invention is related to methods of treating cardiac arrhythmia, angina, or a migraine in a patient in need thereof, with a therapeutically effective amount of a compound having a structure according to the formula: the method comprising nasally administering to the patient (i) a first dose, and (ii) a second dose of an aqueous composition comprising a pharmaceutically acceptable acetate or methanesulfonate salt of compound I, or a racemate or enantiomer thereof, wherein the acetate or methanesulfonate salt of compound I, or the racemate or enantiomer thereof, is dissolved in the aqueous composition at a concentration of 350 mg/mL±50 mg/mL, and wherein the second dose of the compound is administered between 5 minutes and 25 minutes after the first dose.
Inventor(s):	Francis Plat, Douglas WIGHT
Assignee:	Milestone Pharmaceuticals Inc
Application Number:	US17/865,697
Patent Claims:	1. A method of treating a cardiac arrhythmia in a subject in need thereof with a therapeutically effective amount of compound I having a structure according to the formula: the method comprising nasally administering to the subject (i) a first dose, and (ii) a second dose of an aqueous composition comprising a pharmaceutically acceptable acetate or methanesulfonate salt of compound I, or a racemate or enantiomer thereof, wherein the acetate or methanesulfonate salt of compound I, or the racemate or enantiomer thereof, is dissolved in the aqueous composition at a concentration of 350 mg/mL±50 mg/mL, wherein the second dose of the compound is administered between 8 minutes and 16 minutes after the first dose, wherein the first dose and the second dose are the same, and wherein the first and the second dose each comprises between 60 mg and 80 mg of compound I. 2. The method of claim 1, wherein the aqueous composition comprises the acetate salt of compound I. 3. The method of claim 1, wherein the aqueous composition comprises the acetate salt of an S-enantiomer of compound I. 4. The method of claim 1, wherein the cardiac arrhythmia is paroxysmal supraventricular tachycardia (PSVT), atrial fibrillation, or ventricular tachycardia. 5. The method of claim 4, wherein the cardiac arrhythmia is PSVT. 6. The method of claim 4, wherein the cardiac arrhythmia is atrial fibrillation. 7. The method of claim 1, wherein the first and the second dose each comprises no more than two single pump spray dosages. 8. The method of claim 7, wherein each single pump spray dosage comprises 35 mg±3.5 mg of the acetate salt of an S-enantiomer of compound I. 9. The method of claim 8, wherein each of the first and the second dose comprises administering no more than 100 microliters of the aqueous composition to each nostril of the subject. 10. The method of claim 1, wherein the subject is a human. 11. The method of claim 1, wherein the aqueous composition comprises from 40% to 85% (w/v) water. 12. The method of claim 1, wherein the aqueous composition has a pH of 4.5±1.5. 13. The method of claim 1, wherein the aqueous composition further comprises a chelating agent. 14. The method of claim 1, wherein the aqueous composition further comprises EDTA. 15. The method of claim 1, wherein the aqueous composition further comprises a pharmaceutically acceptable excipient. 16. The method of claim 1, wherein the aqueous composition is a homogeneous composition at room temperature. 17. The method of claim 1, wherein the method reduces the heart rate of the subject. 18. The method of claim 1, wherein the aqueous composition comprises the methanesulfonate salt of compound I. 19. The method of claim 7, wherein each single pump spray dosage comprises 35 mg±3.5 mg of the methanesulfonate salt of compound I. 20. The method of claim 1, wherein the second dose of the compound is administered 10±2 minutes after the first dose. 21. The method of claim 1, wherein the second dose of the compound is administered 10±1 minute after the first dose. 22. The method of claim 1, wherein the first and the second dose each comprises 70 mg±10% of compound I.