Claims for Patent: 10,933,136

Summary for Patent: 10,933,136

Title:	Pharmaceutical compositions comprising meloxicam
Abstract:	Disclosed herein are compositions comprising an NSAID such as meloxicam and/or rizatriptan in combination with a cyclodextrin and/or a carbonate or a bicarbonate. These compositions may be orally administered, for example, to improve the bioavailability or pharmacokinetics of the NSAID for the treatment of pain such as migraine, arthritis, and other conditions. Also disclosed herein are methods of treating pain, such as migraine, comprising administering meloxicam and rizatriptan to a human being suffering from pain, such as migraine. For migraine, these methods may be particularly useful when the meloxicam and rizatriptan are administered while the human being is suffering from an acute attack of migraine pain or migraine aura. In some embodiments, the combination of meloxicam and rizatriptan may be administered in a manner that results in a Tmax of meloxicam of 3 hours or less.
Inventor(s):	Herriot Tabuteau
Assignee:	Axsome Therapeutics Inc , Axome Therapeutics Inc
Application Number:	US16/927,623
Patent Claims:	1. A method of treating migraine comprising: selecting a human migraine patient with a history of inadequate response to prior migraine treatments, and orally administering a dosage form to the human migraine patient, wherein the dosage form comprises a combination of: 1) a complex of a meloxicam with a sulfobutyl ether β-cyclodextrin (SBEβCD), 2) a bicarbonate, and 3) a rizatriptan, wherein the human migraine patient has a history of phonophobia accompanying migraine, wherein the human migraine patient is experiencing acute migraine pain with phonophobia at the time the dosage form is orally administered, and wherein the human migraine patient experiences reduction in phonophobia that lasts at least 24 hours after the dosage form is orally administered to the human migraine patient. 2. The method of claim 1, wherein the human migraine patient is selected for having a history of phonophobia accompanying migraine. 3. The method of claim 1, wherein the dosage form contains 400 mg to 600 mg of the bicarbonate. 4. The method of claim 1, wherein the dosage form contains about 5 mg to about 50 mg of the meloxicam. 5. The method of claim 1, wherein the dosage form contains about 50 mg to about 200 mg of the SBEβCD. 6. The method of claim 1, wherein the dosage form is a solid oral dosage form having a shorter Tmax of meloxicam in the human migraine patient than a reference dosage form that: 1) contains the same amount of the meloxicam, 2) does not contain an SBEβCD, and 3) does not contain a bicarbonate. 7. The method of claim 6, wherein the solid oral dosage form has been shown to have faster time to therapeutic plasma concentration in a human being as compared to the reference dosage form. 8. The method of claim 1, wherein about 1 mg to about 50 mg of the rizatriptan is present in the dosage form based upon the weight of rizatriptan in the free base form. 9. The method of claim 1, wherein the rizatriptan is present in a salt form in an amount that is a molar equivalent of about 10 mg of rizatriptan in the free base form. 10. The method of claim 1, wherein the rizatriptan is present as rizatriptan benzoate. 11. The method of claim 1, wherein the dosage form contains about 10 mg to about 30 mg of the meloxicam. 12. The method of claim 1, wherein the dosage form contains about 20 mg of the meloxicam. 13. The method of claim 1, wherein the dosage form contains about 15 mg of the meloxicam. 14. The method of claim 1, wherein the SBEβCD has about 6 to about 7 sulfobutyl ether groups for each molecule of β-cyclodextrin. 15. The method of claim 1, wherein the dosage form contains about 50 mg to about 150 mg of the SBEβCD. 16. The method of claim 1, wherein the dosage form contains about 100 mg of the SBEβCD. 17. The method of claim 1, wherein the molar ratio of the SBEβCD to the meloxicam is about 0.5 to about 2. 18. The method of claim 1, wherein the molar ratio of the SBEβCD to the meloxicam is about 0.8 to about 1.2. 19. The method of claim 1, wherein the molar ratio of the SBEβCD to the meloxicam is about 1. 20. The method of claim 1, wherein the dosage form contains about 10 mg to about 40 mg of the meloxicam, and about 5 mg to about 50 mg of the rizatriptan. 21. The method of claim 1, wherein the dosage form contains the SBEβCD that is in a weight ratio to the rizatriptan that is within a range of about 1 to about 100. 22. The method of claim 1, wherein the dosage form contains the SBEβCD that is in a weight ratio to the rizatriptan that is about 10. 23. The method of claim 1, wherein the bicarbonate comprises sodium bicarbonate. 24. The method of claim 1, wherein the dosage form contains 500 mg of sodium bicarbonate. 25. The method of claim 1, wherein the dosage form has been shown to have a median Tmax of meloxicam that is less than about 90 minutes in fasted human subjects. 26. The method of claim 1, wherein the dosage form has been shown to have a median Tmax of meloxicam that is less than about 2 hours in fasted human subjects. 27. The method of claim 2, wherein the dosage form contains 400 mg to 600 mg of the bicarbonate. 28. The method of claim 2, wherein the dosage form contains about 5 mg to about 50 mg of the meloxicam. 29. The method of claim 2, wherein the dosage form contains about 50 mg to about 200 mg of the SBEβCD. 30. The method of claim 2, wherein the dosage form is a solid oral dosage form having a shorter Tmax of meloxicam in the human migraine patient than a reference dosage form that: 1) contains the same amount of the meloxicam, 2) does not contain an SBEβCD, and 3) does not contain a bicarbonate.