# US 11,998,529 B2 · Non-sedating dexmedetomidine treatment regimens

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- Number: US 11,998,529 B2
- Document ID: US11998529B2
- Status: Granted
- Kind: B2
- Application number: 18/216,890
- Filed: 2023-06-30
- Published: 2023-10-26
- Granted: 2024-06-04
- Earliest claimed: 2019-07-19
- 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/US11998529B2

## 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 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/7007: {Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence)}
- A61K 9/7015: {Drug-containing film-forming compositions, e.g. spray-on}
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 47/38: Cellulose; Derivatives thereof
- A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14)
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/36: Opioid-abuse
- 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 an agitation of a human subject using an oromucosal formulation of dexmedetomidine, the method comprising:
administering an initial dose of the oromucosal formulation of dexmedetomidine or a pharmaceutically acceptable salt thereof to the human subject, wherein the initial dose is 60 mcg, 80 mcg, 90 mcg, 120 mcg, or 180 mcg of dexmedetomidine;
and, after at least two hours,
administering a second dose of the oromucosal formulation of dexmedetomidine or a pharmaceutically acceptable salt thereof to the human subject, wherein the agitation of the human subject is persistent, and wherein the second dose is 40 mcg, 60 mcg, 80 mcg, or 90 mcg of dexmedetomidine, and
wherein the human subject has a corrected OT interval using Fridericia's correction method (QTcF) of less than 470 msec.

### Claim 2 (depends on 1)

The method of claim 1, wherein the initial dose is 60 mcg, 80 mcg, or 90 mcg.

### Claim 3 (depends on 2)

The method of claim 2, wherein the second dose is 40 mcg, 60 mcg, or 80 mcg.

### Claim 4 (depends on 1)

The method of claim 1, wherein the initial dose is 120 mcg or 180 mcg.

### Claim 5 (depends on 4)

The method of claim 4, wherein the second dose is 60 mcg.

### Claim 6 (depends on 4)

The method of claim 4, wherein the second dose is 40 mcg, 60 mcg, or 80 mcg.

### Claim 7 (depends on 1)

The method of claim 1, wherein the second dose is 40 mcg, 60 mcg, or 80 mcg.

### Claim 8 (depends on 1)

The method of claim 1, wherein the second dose is 60 mcg or 90 meg.

### Claim 9 (depends on 1)

The method of claim 1, wherein the second dose is 60 mcg.

### Claim 10 (depends on 1)

The method of claim 1, wherein the initial dose is 120 mcg and the second dose is 60 mcg.

### Claim 11 (depends on 1)

The method of claim 1, wherein the initial dose is 180 mcg and the second dose is 90 mcg.

### Claim 12 (depends on 1)

The method of claim 1, wherein the second dose is administered to a subject having a change in PEC score of less than or equal to 40% following the initial dose.

### Claim 13 (depends on 1)

The method of claim 1, wherein the second dose is administered to a subject having a systolic/diastolic blood pressure greater than 90/60, and a heart rate greater than 60 bpm.

### Claim 14 (depends on 1)

The method of claim 1, wherein the human subject has a QTcF of less than 450 msec.

### Claim 15

A method of treating an agitation of a human subject using an oromucosal formulation of dexmedetomidine, the method comprising:
administering an initial dose of the oromucosal formulation of dexmedetomidine or a pharmaceutically acceptable salt thereof to the human subject, wherein the initial dose is 120 mcg of dexmedetomidine;
and, after at least two hours,
administering a second dose of the oromucosal formulation of dexmedetomidine or a pharmaceutically acceptable salt thereof to the human subject, wherein the second dose is 60 mcg of dexmedetomidine, and
wherein the human subject has a corrected QT interval using Fridericia's correction method (QTcF) of less than 470 msec.

### Claim 16 (depends on 15)

The method of claim 15, wherein the human subject has a QTcF of less than 450 msec.

### Claim 17

A method of treating an agitation of a human subject using an oromucosal formulation of dexmedetomidine, the method comprising:
administering an initial dose of the oromucosal formulation of dexmedetomidine or a pharmaceutically acceptable salt thereof to the human subject, wherein the initial dose is 180 mcg of dexmedetomidine;
and, after at least two hours,
administering a second dose of the oromucosal formulation of dexmedetomidine or a pharmaceutically acceptable salt thereof to the human subject, wherein the second dose is 90 mcg of dexmedetomidine, and
wherein the human subject has a corrected OT interval using Fridericia's correction method (QTcF) of less than 470 msec.

### Claim 18 (depends on 17)

The method of claim 17, wherein the human subject has a QTcF of less than 450 msec.