Liquid tasimelteon formulations and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11759446-B2
Application number	US-202117216427-A
Country	US
Kind code	B2
Filing date	Mar 29, 2021
Priority date	Dec 13, 2019
Publication date	Sep 19, 2023
Grant date	Sep 19, 2023

Abstract

Liquid suspensions of tasimelteon and methods for their use.

First claim

The invention claimed is:

1. A method of treating Smith-Magenis Syndrome (SMS) in a patient in need thereof, the method comprising:
determining a body mass of the patient; and
in the case that the body mass of the patient is equal to or less than 28 kg, administering to the patient, once daily, a first dose of tasimelteon equal to 0.7 mg/kg in a liquid formulation, wherein the method includes shaking the liquid formulation for at least 15 seconds before administering to the patient; or
in the case that the body mass of the patient is greater than 28 kg, administering to the patient, once daily, a second dose of tasimelteon equal to 20 mg.

2. The method of claim 1 , wherein the liquid formulation comprises:
a homogeneous aqueous suspension of tasimelteon;
a suspending agent;
a taste-masking agent;
an opacity-imparting agent; and
a surfactant,
wherein the composition has a viscosity less than or equal to 150 cps and a specific gravity of greater than 1-1.5 under ambient conditions.

3. The method of claim 2 , wherein the suspending agent includes at least one cellulosic suspending agent selected from a group consisting of: methylcellulose, hydroxypropyl methylcellulose (HPMC), sodium carboxypropylmethylcellulose (CPMC), carboxymethylcellulose sodium, and microcrystalline cellulose.

4. The method of claim 3 , wherein the at least one cellulosic suspending agent includes microcrystalline cellulose and carboxymethylcellulose sodium.

5. The method of claim 2 , wherein tasimelteon is present in the liquid formulation at a concentration of:
1 to 6 mg/mL; or
2 to 5 mg/mL; or
1 mg/mL; or
4 mg/mL; and
the suspending agent is microcrystalline cellulose and sodium carboxymethylcellulose and is present in a concentration of:
10 to 30 mg/mL; or
10 to 20 mg/mL; or
20 mg/mL.

6. The method of claim 2 , wherein the liquid formulation comprises:
mannitol as the opacity-imparting agent at a concentration of:
no more than 200 mg/mL; or
less than 200 mg/mL; or
50 to 100 mg/mL; or
100 mg/mL;

sucrose as the taste-masking agent at a concentration of:
no more than 300 mg/mL; or
less than 300 mg/mL; or
150 to 250 mg/mL; or
200 mg/mL; and

polysorbate 80 as the surfactant at a concentration of:
1 to 5 mg/mL; or
1 to 3 mg/mL; or
2 mg/mL.

7. A method of treating Smith-Magenis Syndrome (SMS) in a patient in need thereof, the method comprising:
determining a body mass of the patient; and
in the case that the body mass of the patient is equal to or less than 28 kg, administering to the patient, once daily, a first dose of tasimelteon equal to 0.7 mg/kg in a liquid formulation, wherein the method includes shaking the liquid formulation for at least 30 seconds before administering to the patient; or
in the case that the body mass of the patient is greater than 28 kg, administering to the patient, once daily, a second dose of tasimelteon equal to 20 mg.

8. The method of claim 7 , wherein the liquid formulation comprises:
a homogeneous aqueous suspension of tasimelteon;
a suspending agent;
a taste-masking agent;
an opacity-imparting agent; and
a surfactant,
wherein the composition has a viscosity less than or equal to 150 cps and a specific gravity of greater than 1-1.5 under ambient conditions.

9. The method of claim 8 , wherein the suspending agent includes at least one cellulosic suspending agent selected from a group consisting of: methylcellulose, hydroxypropyl methylcellulose (HPMC), sodium carboxypropylmethylcellulose (CPMC), carboxymethylcellulose sodium, and microcrystalline cellulose.

10. The method of claim 9 , wherein the at least one cellulosic suspending agent includes microcrystalline cellulose and carboxymethylcellulose sodium.

11. The method of claim 8 , wherein tasimelteon is present in the liquid formulation at a concentration of:
1 to 6 mg/mL; or
2 to 5 mg/mL; or
1 mg/mL; or
4 mg/mL; and
the suspending agent is microcrystalline cellulose and sodium carboxymethylcellulose and is present in a concentration of:
10 to 30 mg/mL; or
10 to 20 mg/mL; or
20 mg/mL.

12. The method of claim 8 , wherein the liquid formulation comprises:
mannitol as the opacity-imparting agent at a concentration of:
no more than 200 mg/mL; or
less than 200 mg/mL; or
50 to 100 mg/mL; or
100 mg/mL;

sucrose as the taste-masking agent at a concentration of:
no more than 300 mg/mL; or
less than 300 mg/mL; or
150 to 250 mg/mL; or
200 mg/mL; and

polysorbate 80 as the surfactant at a concentration of:
1 to 5 mg/mL; or
1 to 3 mg/mL; or
2 mg/mL.

13. The method of claim 12 , wherein the liquid formulation further comprises:
a high-intensity sweetener;
an antioxidant;
sodium chloride; and
a flavoring agent.

14. The method of claim 6 , wherein the liquid formulation further comprises:
a high-intensity sweetener;
an antioxidant;
sodium chloride; and
a flavoring agent.

Assignees

• Vanda Pharmaceuticals Inc

Inventors

• Phadke Deepak
• Polymeropoulos Mihael

Classifications

• A61K31/343 Primary

  condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone · CPC title

• A61K9/10 Primary

  Dispersions; Emulsions · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title

• A61K9/0095

  Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006) · CPC title