Cromolyn compositions for treatment of chronic cough due to idiopathic pulmonary fibrosis

• US 10,463,613 B2
• Filed: 02/15/2019
• Issued: 11/05/2019
• Est. Priority Date: 08/31/2016
• Status: Active Grant

• Current Assignee: Respivant Sciences GmbH
• Original Assignee: Respivant Sciences GmbH
• Inventors: Soni, Pravin, Gerhart, William, Tutuncu, Ahmet
• Primary Examiner(s): Berrios, Jennifer A
• Application Number:
  US16/277,689
• Publication Number:
  US 20190175503A1
• Time in Patent Office: 263 Days
• Field of Search: None
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• CPC Class Codes: A61M 11/005 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14

Abstract

The disclosure provides a method of treating chronic cough in a subject having idiopathic pulmonary fibrosis (IPF) comprising administering to the subject a pharmaceutical composition comprising from about 2% by weight to about 6% by weight of cromolyn sodium and an ionic osmotic agent with a nebulizer.

Claims

1. A method of treating chronic cough in a subject having idiopathic pulmonary fibrosis, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising cromolyn, or a pharmaceutically acceptable salt thereof, with an inhalation device, wherein prior to administration of the pharmaceutical composition the subject has been diagnosed as having chronic cough due to idiopathic pulmonary fibrosis or chronic idiopathic cough and wherein the pharmaceutical composition is administered to the subject only if the subject has been diagnosed as having chronic cough due to idiopathic pulmonary fibrosis.

2. The method of claim 1, wherein the inhalation device is selected from a nebulizer, a dry powder inhaler, and a jet nebulizer.

3. The method of claim 1, wherein the inhalation device is a nebulizer.

4. The method of claim 1, wherein the inhalation device is a dry powder inhaler.

5. The method of claim 1, wherein the inhalation device is a jet nebulizer.

6. The method of claim 1, wherein the composition comprises a pharmaceutically acceptable salt of cromolyn.

7. The method of claim 6, wherein the composition comprises cromolyn sodium.

8. The method of claim 1, wherein the subject is administered one or more doses of cromolyn or a pharmaceutically acceptable salt thereof.

9. The method of claim 1, wherein the subject is administered one or more doses of cromolyn sodium.

10. The method of claim 9, wherein the subject is administered more than one dose of cromolyn sodium.

11. The method of claim 9, wherein each of the one or more doses of cromolyn sodium comprise from about 1 mg to about 120 mg of cromolyn sodium, inclusive of the endpoints.

12. The method of claim 11, wherein each of the one or more doses of cromolyn sodium comprises from about 5 mg to about 80 mg of cromolyn sodium.

13. The method of claim 1, wherein the pharmaceutical composition comprises greater than 1% by weight of cromolyn, or a pharmaceutically acceptable salt thereof.

14. The method of claim 13, wherein the pharmaceutical composition comprises greater than 1% by weight of a pharmaceutically acceptable salt of cromolyn.

15. The method of claim 14, wherein the pharmaceutical composition comprises greater than 1% by weight of cromolyn sodium.

16. The method of claim 15, wherein the pharmaceutical composition comprises about 2% by weight of cromolyn sodium.

17. The method of claim 15, wherein the pharmaceutical composition comprises about 4% by weight of cromolyn sodium.

18. The method of claim 15, wherein the pharmaceutical composition comprises about 6% by weight of cromolyn sodium.

19. The method according to claim 1, wherein the pharmaceutical composition is administered to the subject from once to five times per day.

20. The method according to claim 1, wherein the pharmaceutical composition is administered to the subject three times per day.

21. The method according to claim 20, wherein the pharmaceutical composition is administered to the subject for 14 days or more.

22. The method of claim 1, wherein administration of the pharmaceutical composition to the subject with the inhalation device provides in the subject a bioavailability of cromolyn greater than about 5%.

23. The method of claim 2, wherein administration of the pharmaceutical composition to the subject with the inhalation device provides in the subject a bioavailability of cromolyn greater than about 5%.

24. The method of claim 1, wherein the subject is administered one or more doses of the pharmaceutical composition comprising greater than 1% by weight of cromolyn sodium and the inhalation device is a nebulizer.

25. The method of claim 24, wherein each of the doses of the pharmaceutical composition comprises from about 5 mg to about 80 mg of cromolyn sodium, and administration of the pharmaceutical composition provides in the subject a deposited lung dose of cromolyn in the subject of about 0.5 mg to about 8.0 mg.

26. The method of claim 24, wherein each of the doses of the pharmaceutical composition comprises from about 10 mg to about 80 mg of cromolyn sodium, and administration of the pharmaceutical composition provides in the subject an AUC_(0-∞

) of the cromolyn sodium of from 100 ng*hr/mL to 500 ng*hr/mL.

27. The method of claim 24, wherein each of the doses of the pharmaceutical composition comprises from about 20 mg to about 80 mg of cromolyn sodium, and administration of the pharmaceutical composition provides in the subject a C_max of the cromolyn sodium of from 50 ng/mL to 230 ng/mL.

28. The method of claim 1, wherein the inhalation device is a nebulizer, and the pharmaceutical composition consists of cromolyn sodium, sodium chloride, sodium EDTA and water.

29. The method of claim 28, wherein the cromolyn sodium in the pharmaceutical composition is present at a concentration of from about 2% by weight to about 6% weight.

30. The method of claim 28, wherein the cromolyn sodium in the pharmaceutical composition is present at a concentration of from about 2% by weight to about 6% weight, and the nebulizer produces an aerosol of the pharmaceutical composition that exhibits a respirable fraction (≤

5 μ

m) as measured by USP <

1601>

of at least about 60%.