# US 11,998,528 B1 · Non-sedating dexmedetomidine treatment regimens

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- Number: US 11,998,528 B1
- Document ID: US11998528B1
- Status: Granted
- Kind: B1
- Application number: 18/189,073
- Filed: 2023-03-23
- Granted: 2024-06-04
- Earliest claimed: 2023-01-12
- Assignees: BioXcel Therapeutics, Inc.
- Applicants: BioXcel Therapeutics, Inc.
- Inventors: Vasukumar Kakumanu; David Christian Hanley; Frank Yocca; Chetan Dalpatbhai Lathia; Lavanya Rajachandran; Robert Risinger
- Web page: https://patentgrep.com/patent/US11998528B1

## CPC

- A61K 31/4174: Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
- A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/20: Hypnotics; Sedatives
- 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 methods of administering relatively high doses of dexmedetomidine or a pharmaceutically acceptable salt thereof to a human subject, without also inducing significant sedation. The disclosed methods are particularly suitable for the treatment of agitation, especially when associated with neurodegenerative and/or neuropsychiatric diseases such as schizophrenia, bipolar illness such as bipolar disorder or mania, dementia, depression, or delirium.

## Claims

### Claim 1

A method of treating acute agitation associated with schizophrenia or bipolar disorder in an agitated human subject at risk of torsades de pointes or sudden death, comprising:
administering dexmedetomidine or a pharmaceutically acceptable salt thereof in an oromucosal formulation up to a maximum dosing regimen;
wherein the maximum dosing regimen is a single dose of 120 mcg of dexmedetomidine when a maximum allowed QT prolongation is less than 7 msec;
wherein the maximum dosing regimen is a single dose of 120 mcg of dexmedetomidine plus 1 or 2 additional doses of 60 mcg at least 2 hours apart when a maximum allowed QT prolongation is less than 9 msec but no less than 7 msec;
wherein the maximum dosing regimen is a single dose of 180 mcg of dexmedetomidine when a maximum allowed QT prolongation is less than 11 msec but no less than 9 msec; and
wherein the maximum dosing regimen is a single dose of 180 mcg of dexmedetomidine plus 1 or 2 additional doses of 90 mcg at least 2 hours apart when a maximum allowed QT prolongation is less than 14 msec but no less than 11 msec.

### Claim 2 (depends on 1)

The method of claim 1, wherein the maximum allowed QT prolongation is further based on at least one risk factor for the risk of torsades de pointes or sudden death.

### Claim 3 (depends on 2)

The method of claim 2, wherein the at least one risk factor is a known QT prolongation of the agitated human subject.

### Claim 4 (depends on 2)

The method of claim 2, wherein the at least one risk factor is a history of other arrhythmias of the agitated human subject.

### Claim 5 (depends on 2)

The method of claim 2, wherein the at least one risk factor is a symptomatic bradycardia of the agitated human subject.

### Claim 6 (depends on 2)

The method of claim 2, wherein the at least one risk factor is a hypokalemia of the agitated human subject.

### Claim 7 (depends on 2)

The method of claim 2, wherein the at least one risk factor is a hypomagnesemia of the agitated human subject.

### Claim 8 (depends on 2)

The method of claim 2, wherein the at least one risk factor is additional drugs that prolong the QT interval of the agitated human subject.

### Claim 9 (depends on 3)

The method of claim 3, wherein the at least one risk factor comprises a history of other arrhythmias, a symptomatic bradycardia, hypokalemia or hypomagnesemia, and additional drugs known to prolong the QT interval of the agitated human subject.

### Claim 10

A method of treating acute agitation associated with schizophrenia or bipolar disorder in an agitated human subject at risk of torsades de pointes or sudden death, comprising:
administering dexmedetomidine or a pharmaceutically acceptable salt thereof in an oromucosal formulation up to a maximum dosing regimen;
wherein the maximum dosing regimen is a single dose of 120 mcg of dexmedetomidine when a maximum allowed QT prolongation is less than 6 msec;
wherein the maximum dosing regimen is a single dose of 120 mcg of dexmedetomidine plus 1 or 2 additional doses of 60 mcg at least 2 hours apart when a maximum allowed QT prolongation is less than 8 msec but no less than 6 msec;
wherein the maximum dosing regimen is a single dose of 180 mcg of dexmedetomidine when a maximum allowed QT prolongation is less than 8 msec but no less than 6 msec; and
wherein the maximum dosing regimen is a single dose of 180 mcg of dexmedetomidine plus 1 or 2 additional doses of 90 mcg at least 2 hours apart when a maximum allowed QT prolongation is less than 11 msec but no less than 8 msec.

### Claim 11 (depends on 10)

The method of claim 10, wherein the maximum allowed QT prolongation of the agitated human subject is further based on at least one risk factor for the risk of torsades de pointes or sudden death.

### Claim 12 (depends on 11)

The method of claim 11, wherein the at least one risk factor is a known QT prolongation of the agitated human subject.

### Claim 13 (depends on 11)

The method of claim 11, wherein the at least one risk factor is a history of other arrhythmias of the agitated human subject.

### Claim 14 (depends on 11)

The method of claim 11, wherein the at least one risk factor is a symptomatic bradycardia of the agitated human subject.

### Claim 15 (depends on 11)

The method of claim 11, wherein the at least one risk factor is a hypokalemia of the agitated human subject.

### Claim 16 (depends on 11)

The method of claim 11, wherein the at least one risk factor is a hypomagnesemia of the agitated human subject.

### Claim 17 (depends on 11)

The method of claim 11, wherein the at least one risk factor is additional drugs that prolong the QT interval of the agitated human subject.

### Claim 18 (depends on 12)

The method of claim 12, wherein the at least one risk factor comprises a history of other arrhythmias, a symptomatic bradycardia, hypokalemia or hypomagnesemia, and additional drugs that prolong the QT interval of the agitated human subject.