# US 11,077,117 B2 · Pharmaceutical compositions comprising meloxicam

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- Number: US 11,077,117 B2
- Document ID: US11077117B2
- Status: Granted
- Kind: B2
- Application number: 17/148,342
- Filed: 2021-01-13
- Published: 2021-05-06
- Granted: 2021-08-03
- Earliest claimed: 2017-01-04
- Assignees: Axsome Therapeutics, Inc.
- Applicants: Axsome Therapeutics, Inc.
- Inventors: Herriot Tabuteau
- Web page: https://patentgrep.com/patent/US11077117B2

## CPC

- A61K 31/5415: ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/2009: {Inorganic compounds}
- A61K 9/205: {Polysaccharides, e.g. alginate, gums; Cyclodextrin}
- A61K 9/2086: {Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat (active cores with a complete drug-free outer coat A61K9/28)}
- 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 47/02: Inorganic compounds
- A61K 47/40: Cyclodextrins; Derivatives thereof
- A61K 47/6951: {using cyclodextrin (cyclodextrins used as simple excipients A61K47/40)}
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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

## 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 relieving migraine pain, comprising: orally administering to a human being in need thereof, a combination of: 1) a complex of a meloxicam and a sulfobutylether-β-cyclodextrin, 2) a bicarbonate, and 3) a rizatriptan, wherein the combination is orally administered when the human being is suffering from moderate to severe migraine pain of an acute migraine, wherein the combination comprises: about 5 mg to about 50 mg of the meloxicam in the free base form, or a molar equivalent of a salt form; about 8 mg to about 30 mg of the rizatriptan in the free base form or a molar equivalent of a salt form, and 400 mg to 1000 mg of the bicarbonate, 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 one hour after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience one hour 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 twenty four hours after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience twenty four 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 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 10 (depends on 1)

The method of claim 1, 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 base form, or a molar equivalent of a salt form; and 400 mg to 600 mg of the bicarbonate.

### Claim 11 (depends on 10)

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

### Claim 12 (depends on 10)

The method of claim 10, 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 13 (depends on 12)

The method of claim 12, wherein the human being has a history of inadequate response to prior migraine treatments.

### Claim 14 (depends on 12)

The method of claim 12, wherein the human being is selected for having a history of inadequate response to prior migraine treatments.

### Claim 15 (depends on 12)

The method of claim 12, 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 16 (depends on 12)

The method of claim 12, wherein twenty four hours after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience twenty four hours after the same amount of the rizatriptan is orally administered alone.

### 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 1)

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

### Claim 19 (depends on 1)

The method of claim 1, wherein the human being achieves absence of the most bothersome symptom to the human being two hours after the combination is orally administered, and wherein the most bothersome symptom is nausea, phonophobia, or photophobia.

### Claim 20 (depends on 1)

The method of claim 1, 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 21 (depends on 1)

The method of claim 1, wherein the human being has migraine pain that is accompanied with nausea.

### Claim 22 (depends on 21)

The method of claim 21, 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 23 (depends on 1)

The method of claim 1, wherein the bicarbonate is sodium bicarbonate.

### Claim 24 (depends on 1)

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

### Claim 25 (depends on 1)

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

### Claim 26 (depends on 1)

The method of claim 1, wherein the complex of the meloxicam and the sulfobutylether-β-cyclodextrin, the bicarbonate, and the rizatriptan are present in a single dosage form.

### Claim 27 (depends on 1)

The method of claim 1, wherein migraine pain is accompanied by disturbed vision.

### Claim 28 (depends on 27)

The method of claim 27, wherein the human being achieves absence of the disturbed vision two hours after the combination is orally administered.