Methods of treatment for cystic fibrosis

Patent metadata

Field	Value
Publication number	US-11253509-B2
Application number	US-201816620265-A
Country	US
Kind code	B2
Filing date	Jun 8, 2018
Priority date	Jun 8, 2017
Publication date	Feb 22, 2022
Grant date	Feb 22, 2022

Abstract

Compound I of the formula (formula) A pharmaceutically acceptable salt of Compound I. Pharmaceutical compositions containing at least Compound I and methods of treating cystic fibrosis comprising administering at least Compound I. Pharmaceutical compositions containing a pharmaceutically acceptable salt of at least Compound I and methods of treating cystic fibrosis comprising administering a pharmaceutically acceptable salt of at least Compound I.

First claim

The invention claimed is:

1. A method of treating cystic fibrosis comprising administering daily to a patient in need thereof:
(A) 80 mg to 400 mg of at least one compound chosen from Compound I:

and pharmaceutically acceptable salts thereof; and
(B) at least one compound chosen from:
(i) Compound II:

and pharmaceutically acceptable salts thereof,
(ii) Compound III:

and pharmaceutically acceptable salts thereof, or
Compound III-d:

and pharmaceutically acceptable salts thereof, and
(iii) Compound IV:

and pharmaceutically acceptable salts thereof.

2. The method according to claim 1 , comprising administering to said patient:
(A) at least one compound chosen from Compound I and pharmaceutically acceptable salts thereof; and at least one compound chosen from Compound II and pharmaceutically acceptable salts thereof;
(B) at least one compound chosen from Compound I and pharmaceutically acceptable salts thereof; and at least one compound chosen from (i) Compound III and pharmaceutically acceptable salts thereof, or (ii) Compound III-d and pharmaceutically acceptable salts thereof; or
(C) at least one compound chosen from Compound I and a pharmaceutically acceptable salts thereof; and at least one compound chosen from Compound IV and pharmaceutically acceptable salts thereof.

3. The method according to claim 1 , comprising administering to said patient:
(A) at least one compound chosen from Compound I and pharmaceutically acceptable salts thereof;
(B) at least one compound chosen from (i) Compound III and pharmaceutically acceptable salts thereof, or (ii) Compound III-d and pharmaceutically acceptable salts thereof; and
(C) at least one compound chosen from Compound IV and pharmaceutically acceptable salts thereof.

4. The method of according to claim 1 , comprising administering to said patient:
(A) at least one compound chosen from Compound I and pharmaceutically acceptable salts thereof;
(B) at least one compound chosen from Compound II and pharmaceutically acceptable salts thereof; and
(C) at least one compound chosen from Compound III and pharmaceutically acceptable salts thereof.

5. The method of according to claim 1 , comprising administering to said patient:
(A) at least one compound chosen from Compound I and pharmaceutically acceptable salts thereof;
(B) at least one compound chosen from Compound II and pharmaceutically acceptable salts thereof; and
(C) at least one compound chosen from Compound III-d and pharmaceutically acceptable salts thereof.

6. The method according to claim 1 , wherein 120 mg to 240 mg of Compound I or a pharmaceutically acceptable salt thereof is administered daily.

7. The method according to claim 1 , wherein 120 mg to 360 mg of Compound I or a pharmaceutically acceptable salt thereof is administered daily.

8. The method according to claim 1 , wherein 120 mg of Compound I or a pharmaceutically acceptable salt thereof is administered daily.

9. The method according to claim 1 , wherein 240 mg of Compound I or a pharmaceutically acceptable salt thereof is administered daily.

10. The method according to claim 1 wherein 120 mg of Compound I or a pharmaceutically acceptable salt thereof per dosing is administered twice daily.

11. The method according to claim 1 , wherein 50 mg to 150 mg of Compound II or a pharmaceutically acceptable salt thereof is administered daily.

12. The method according to claim 1 , wherein 100 mg of Compound II or a pharmaceutically acceptable salt thereof is administered daily.

13. The method according to claim 1 , wherein:
(i) 50 mg to 600 mg of Compound III or a pharmaceutically acceptable salt thereof is administered daily; or
(ii) 50 mg to 600 mg of Compound III-d or a pharmaceutically acceptable salt thereof is administered daily.

14. The method according to claim 1 , wherein: (i) 125 mg to 300 mg of Compound III or a pharmaceutically acceptable salt thereof is administered daily; or (ii) 125 mg to 300 mg of Compound III-d or a pharmaceutically acceptable salt thereof is administered daily.

15. The method according to claim 1 , wherein: (i) 75 mg of Compound III or a pharmaceutically acceptable salt thereof per dosing is administered twice daily; or (ii) 100 mg of Compound III-d or a pharmaceutically acceptable salt thereof is administered per dosing once daily.

16. The method according to claim 1 , wherein 400 mg to 1,000 mg of Compound IV or a pharmaceutically acceptable salt thereof is administered daily.

17. The method according to claim 1 , wherein:
(A) 50 mg to 200 mg of at least one compound chosen from Compound II and pharmaceutically acceptable salts thereof is administered daily and/or 150 mg to 600 mg of at least one compound chosen from Compound III and pharmaceutically acceptable salts thereof is administered daily; or
(B) 50 mg to 200 mg of at least one compound chosen from Compound II and pharmaceutically acceptable salts thereof is administered daily and/or 100 mg to 400 mg of at least one compound chosen from Compound III-d and pharmaceutically acceptable salts thereof is administered daily.

18. The method according to claim 1 , wherein the at least one compound chosen from Compound I and pharmaceutically acceptable salts thereof is Compound I.

19. The method according to claim 1 , wherein the at least one compound chosen from Compound I and pharmaceutically acceptable salts thereof is a pharmaceutically acceptable salt of Compound I.

20. A method of treating cystic fibrosis comprising administering daily to a patient in need thereof:
(A) 50 mg to 300 mg of Compound I:

or a pharmaceutically acceptable salt thereof daily; 50 mg of Compound II:

or a pharmaceutically acceptable salt thereof; and 150 mg or 300 mg of Compound III:

or a pharmaceutically acceptable salt thereof; or
(B) 50 mg to 300 mg of Compound I or a pharmaceutically acceptable salt thereof; 50 mg of Compound II or a pharmaceutically acceptable salt thereof; and 150 mg, 200 mg, or 300 mg of Compound III-d:

or a pharmaceutically acceptable salt thereof.

21. The method according to claim 20 , wherein:
(A) 120 mg of Compound I or a pharmaceutically acceptable salt thereof; 50 mg of Compound II or a pharmaceutically acceptable salt thereof; and 150 mg of Compound III or a pharmaceutically acceptable salt thereof are administered daily; or
(B) 120 mg of Compound I or a pharmaceutically salt thereof; 50 mg of

Assignees

• Vertex Pharma

Inventors

• Chen Weichao George
• Haseltine Eric L
• Moskowitz Samuel
• Robertson Sarah
• Waltz David

Classifications

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61K31/4045

  Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin · CPC title

• A61K31/443

  containing a five-membered ring with oxygen as a ring hetero atom · CPC title

• A61K31/47 Primary

  Quinolines; Isoquinolines · CPC title

• A61K31/454 Primary

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title