# US 11,433,079 B2 · Pharmaceutical compositions comprising meloxicam > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,433,079 B2 - Document ID: US11433079B2 - Status: Granted - Kind: B2 - Application number: 17/549,081 - Filed: 2021-12-13 - Published: 2022-04-07 - Granted: 2022-09-06 - Earliest claimed: 2017-01-04 - Assignees: Axsome Therapeutics, Inc. - Applicants: Axsome Therapeutics, Inc. - Inventors: Herriot Tabuteau - Web page: https://patentgrep.com/patent/US11433079B2 ## CPC - A61K 9/2009: {Inorganic compounds} - A61K 31/5415: ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam - A61K 9/209: {containing drug in at least two layers or in the core and in at least one outer layer} - A61K 31/4196: 1,2,4-Triazoles - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61K 47/02: Inorganic compounds - A61K 47/61: the organic macromolecular compound being a polysaccharide or a derivative thereof - A61K 47/6951: {using cyclodextrin (cyclodextrins used as simple excipients A61K47/40)} - A61P 1/08: for nausea, cinetosis or vertigo; Antiemetics - A61P 25/06: Antimigraine agents - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES ## 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. ## Claims ### Claim 1 A method of treating migraine, comprising orally administering a combination to a human being who is experiencing an acute attack of migraine pain or migraine aura, wherein the combination comprises a meloxicam and about 8 mg to about 13 mg of a rizatriptan based upon the weight of the free base form of rizatriptan, wherein the combination is in a single dosage form, wherein the single dosage form is structured so that orally administering the single dosage form to healthy human subjects would result in a mean Tmax of meloxicam of 110 minutes or less, and an AUC0-24 of meloxicam of about 30 μg·hr/mL to about 50 μg·hr/mL, wherein the combination is orally administered when the human being is experiencing moderate to severe migraine pain of an acute migraine, and wherein the human being experiences improvement in migraine symptoms, as determined by the Patient Global Impression of Change (PGI-C), at twenty-four hours after the combination is orally administered. ### Claim 2 (depends on 1) The method of claim 1, wherein two hours after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience two hours after the same amount of the rizatriptan is orally administered alone. ### Claim 3 (depends on 1) The method of claim 1, wherein two hours after the combination is orally administered, the human being experiences a greater reduction in the human being's most bothersome symptom than the human being would experience two hours after the same amount of the rizatriptan is orally administered alone, and wherein the most bothersome symptom is nausea, phonophobia, or photophobia. ### Claim 4 (depends on 1) The method of claim 1, wherein the human being has a history of inadequate response to prior migraine treatments. ### Claim 5 (depends on 1) The method of claim 1, wherein the human being is selected for having a history of inadequate response to prior migraine treatments. ### Claim 6 (depends on 1) The method of claim 1, wherein the human being has had an average of about 2 to about 8 moderate to severe migraine attacks per month. ### Claim 7 (depends on 1) The method of claim 1, wherein the human being is selected for having an average of about 2 to about 8 moderate to severe migraine attacks per month. ### Claim 8 (depends on 1) The method of claim 1, wherein the meloxicam is complexed with a sulfobutylether-β-cyclodextrin. ### Claim 9 (depends on 8) The method of claim 8, wherein the combination further comprises a bicarbonate. ### Claim 10 (depends on 1) The method of claim 1, wherein the combination further comprises a bicarbonate. ### Claim 11 (depends on 9) The method of claim 9, wherein the combination contains: about 10 mg of rizatriptan in the free base form or a molar equivalent of a salt form; about 20 mg of meloxicam in the free acid form, or a molar equivalent of a salt form; and about 400 mg to about 600 mg of the bicarbonate. ### Claim 12 (depends on 11) The method of claim 11, wherein the bicarbonate is sodium bicarbonate. ### Claim 13 (depends on 11) The method of claim 11, wherein thirty minutes after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience thirty minutes after the same amount of the rizatriptan is orally administered alone. ### Claim 14 (depends on 13) The method of claim 13, wherein the human being has a history of inadequate response to prior migraine treatments. ### Claim 15 (depends on 13) The method of claim 13, wherein the human being is selected for having a history of inadequate response to prior migraine treatments. ### Claim 16 (depends on 13) The method of claim 13, wherein 1) the complex of the meloxicam and the sulfobutylether-β-cyclodextrin, 2) the bicarbonate, and 3) the rizatriptan, are combined together in a monolayer tablet. ### Claim 17 (depends on 1) The method of claim 1, wherein the human being does not take any rescue medication for at least twenty-four hours after the combination is orally administered. ### Claim 18 (depends on 11) The method of claim 11, wherein the complex of the meloxicam and the sulfobutylether-β-cyclodextrin are present in a dosage form with the bicarbonate, and the bicarbonate is present in an amount that is effective to increase the dissolution rate of meloxicam. ### Claim 19 (depends on 1) The method of claim 1, wherein the human being has migraine pain that is accompanied with nausea. ### Claim 20 (depends on 19) The method of claim 19, wherein two hours after the combination is orally administered, the human being experiences a greater reduction in nausea than the human being would experience two hours after the same amount of the rizatriptan is orally administered alone. ### Claim 21 (depends on 11) The method of claim 11, wherein the bicarbonate is sodium bicarbonate. ### Claim 22 (depends on 1) The method of claim 1, wherein the meloxicam is in the free acid form. ### Claim 23 (depends on 1) The method of claim 1, wherein the rizatriptan is rizatriptan benzoate. ### Claim 24 (depends on 11) The method of claim 11, wherein the complex of the meloxicam and the sulfobutylether-β-cyclodextrin, the bicarbonate, and the rizatriptan are present in a single dosage form. ### Claim 25 (depends on 11) The method of claim 11, wherein migraine pain is accompanied by disturbed vision. ### Claim 26 (depends on 25) The method of claim 25, wherein the human being achieves absence of the disturbed vision two hours after the combination is orally administered. ### Claim 27 (depends on 1) The method of claim 1, wherein the human being is more likely to experience the improvement in the PGI-C at two hours after the combination is orally administered as compared to orally taking a placebo. ### Claim 28 (depends on 1) The method of claim 1, wherein the human being experiences more improvement in the PGI-C at two hours after the combination is orally administered than the human being would have experienced after administering the rizatriptan alone. ### Claim 29 (depends on 1) The method of claim 1, wherein the human being is more likely to return to normal functioning at 24 hours after the combination is orally administered as compared to orally taking a placebo. ### Claim 30 (depends on 1) The method of claim 1, wherein the human being is more likely to return to normal functioning at 24 hours after the combination is orally administered as compared to orally taking the same amount of the rizatriptan alone.