# US 11,433,078 B2 · Pharmaceutical compositions comprising meloxicam

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- Number: US 11,433,078 B2
- Document ID: US11433078B2
- Status: Granted
- Kind: B2
- Application number: 17/544,365
- Filed: 2021-12-07
- Published: 2022-03-24
- 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/US11433078B2

## CPC

- A61K 9/2009: {Inorganic compounds}
- A61K 31/5415: ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
- A61K 9/205: {Polysaccharides, e.g. alginate, gums; Cyclodextrin}
- A61K 31/4196: 1,2,4-Triazoles
- A61K 33/00: Medicinal preparations containing inorganic active ingredients
- A61K 47/02: Inorganic compounds
- A61K 47/40: Cyclodextrins; Derivatives thereof
- A61K 47/6951: {using cyclodextrin (cyclodextrins used as simple excipients A61K47/40)}
- A61P 25/06: Antimigraine agents
- C08B 37/0015: {Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes}
- C08L 5/16: Cyclodextrin; Derivatives thereof
- 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
- C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## 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 suffering from 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, and wherein 1.5 hours after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience 1.5 hours after the same amount of the rizatriptan is orally administered alone.

### Claim 2 (depends on 1)

The method of claim 1, wherein the human being is instructed to take the combination when the human being is suffering from an acute attack of migraine pain or migraine aura.

### Claim 3 (depends on 1)

The method of claim 1, wherein 30 minutes after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience 30 minutes after the same amount of the rizatriptan is orally administered alone.

### Claim 4 (depends on 1)

The method of claim 1, wherein 2 hours after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience 2 hours after the same amount of the rizatriptan is orally administered alone, and wherein 24 hours after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience 24 hours after the same amount of the rizatriptan is orally administered alone.

### Claim 5 (depends on 1)

The method of claim 1, wherein the human being has a history of inadequate response to prior migraine treatments.

### Claim 6 (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 7 (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 8 (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 9 (depends on 1)

The method of claim 1, wherein the meloxicam is complexed with a sulfobutylether-β-cyclodextrin.

### Claim 10 (depends on 9)

The method of claim 9, wherein the combination further comprises a bicarbonate.

### Claim 11 (depends on 1)

The method of claim 1, wherein the combination further comprises a bicarbonate.

### Claim 12 (depends on 10)

The method of claim 10, 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 13 (depends on 10)

The method of claim 10, 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 14 (depends on 13)

The method of claim 13, wherein the bicarbonate is sodium bicarbonate.

### Claim 15 (depends on 13)

The method of claim 13, wherein 30 minutes after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience 30 minutes after the same amount of the rizatriptan is orally administered alone.

### Claim 16 (depends on 15)

The method of claim 15, wherein the human being has a history of inadequate response to prior migraine treatments.

### Claim 17 (depends on 15)

The method of claim 15, wherein the human being is selected for having a history of inadequate response to prior migraine treatments.

### Claim 18 (depends on 15)

The method of claim 15, 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 19 (depends on 15)

The method of claim 15, wherein 2 hours after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience 2 hours after the same amount of the rizatriptan is orally administered alone, and wherein 24 hours after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience 24 hours after the same amount of the rizatriptan is orally administered alone.

### Claim 20 (depends on 1)

The method of claim 1, wherein the human being does not take any rescue medication for at least 24 hours after the combination is orally administered.

### Claim 21 (depends on 10)

The method of claim 10, wherein the bicarbonate is present in an amount that is effective to increase the dissolution rate of meloxicam.

### Claim 22 (depends on 1)

The method of claim 1, wherein the human being is also suffering from nausea.

### Claim 23 (depends on 22)

The method of claim 22, wherein 2 hours after the combination is orally administered, the human being experiences a greater reduction in nausea than the human being would experience 2 hours after the same amount of the rizatriptan is orally administered alone.

### Claim 24 (depends on 10)

The method of claim 10, wherein the bicarbonate is sodium bicarbonate.

### Claim 25 (depends on 11)

The method of claim 11, wherein the bicarbonate is sodium bicarbonate.

### Claim 26 (depends on 1)

The method of claim 1, wherein the meloxicam is in the free acid form.

### Claim 27 (depends on 1)

The method of claim 1, wherein the rizatriptan is rizatriptan benzoate.

### Claim 28 (depends on 1)

The method of claim 1, wherein the migraine pain is accompanied by disturbed vision, and wherein the human being achieves absence of the disturbed vision 2 hours after the combination is orally administered.

### Claim 29 (depends on 1)

The method of claim 1, wherein the human being achieves pain freedom 1.5 hours after the combination is orally administered.

### Claim 30 (depends on 1)

The method of claim 1, wherein the reduction of migraine pain of the human being is assessed 1.5 hours after the combination is orally administered to the human being.