Methods of treating schizophrenia

Patent metadata

Field	Value
Publication number	US-11129807-B2
Application number	US-201816486257-A
Country	US
Kind code	B2
Filing date	Feb 16, 2018
Priority date	Feb 16, 2017
Publication date	Sep 28, 2021
Grant date	Sep 28, 2021

Abstract

Provided herein are methods for determining if a compound has potential efficacy for the treatment for a specific symptom domain of schizophrenia, such as for example, the treatment of a negative symptom of schizophrenia. In addition, provided herein are methods of determining the prominent symptom domain of a subject suffering from schizophrenia. Further, provided herein are various methods for the treatment of the negative symptoms, cognitive dysfunction symptoms, or both, associated with schizophrenia comprising administering to a subject a therapeutically or prophylactically effective amount of various compounds.

First claim

What is claimed:

1. A method for treating a subject having prominently negative symptoms of schizophrenia comprising administering to the subject a therapeutically effective amount of the compound

or a pharmaceutically acceptable salt thereof, for four weeks to a subject in need thereof, wherein the subject experiences a decrease in negative PANSS score after four weeks of administration.

2. The method of claim 1 , wherein the method further comprises a step of determining if a subject exhibits prominently negative symptoms by:
(a) transforming baseline PANSS factor scores for the subject using a score matrix in accord with Table 4A;
(b) determining transformed PANSS symptom domain scores;
(c) comparing the transformed PANSS symptom domain scores and determining that the subject exhibits prominently negative symptoms if the transformed PANSS negative domain score is the highest transformed PANSS symptom domain score.

3. The method of claim 1 , wherein the method further comprises a step of determining if a subject exhibits prominently negative symptoms by:
(a) transforming baseline PANSS factor scores for the subject using a score matrix in accord with Table 4A;
(b) determining transformed PANSS symptom domain scores;
(c) determining a subject has prominently negative symptoms by comparing the transformed PANSS symptom domain scores to a score associated with a prominent negative symptom sub-population.

4. The method of claim 1 , wherein the therapeutically effective amount is an amount between about 10 mg and about 300 mg.

5. The method of claim 1 , wherein the therapeutically effective amount is an amount between about 20 mg and about 250 mg.

6. The method of claim 1 , wherein the therapeutically effective amount is an amount between about 10 mg and about 100 mg.

7. The method of claim 1 , wherein the therapeutically effective amount is an amount between about 25 mg and about 50 mg.

8. The method of claim 1 , wherein the therapeutically effective amount is provided as a once daily dose.

9. The method of claim 1 , further comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising the compound

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

10. A method for treating schizophrenia comprising administering a therapeutically effective amount of a compound

or a pharmaceutically acceptable salt thereof, for four weeks to a subject in need thereof, wherein the subject experiences a decrease in negative PANSS score after four weeks of administration.

11. The method of claim 10 , wherein the negative PANSS score is determined by negative PANSS factors N01 Blunted Affect, N02 Emotional Withdrawal, N03 Poor Rapport, N04 Passive/Apathetic Social Withdrawal, N05 Difficulty in Abstract Thinking, N06 Lack of Spontaneity and Flow of Conversation, and N07 Stereotyped Thinking.

12. The method of claim 10 , wherein the subject experiences a decrease of at least 10% from baseline in negative PANSS score after four weeks of administration.

13. The method of claim 12 , wherein the subject experiences a decrease of at least 20% from baseline in negative PANSS score after four weeks of administration.

14. A method for treating schizophrenia comprising administering a therapeutically effective amount of a compound

or a pharmaceutically acceptable salt thereof, for four weeks to a subject in need thereof, wherein the subject experiences a decrease in negative symptoms, cognitive dysfunction symptoms, or both, associated with schizophrenia after four weeks of administration.

15. The method of any one of claims 10 - 14 wherein the compound is administered once daily.

16. The method of any one of claims 10 - 14 wherein the compound is orally administered once daily.

17. The method of any one of claims 10 - 14 wherein the therapeutically effective amount is from about 10 mg to about 300 mg per day.

18. The method of any one of claims 10 - 14 wherein the therapeutically effective amount is from about 20 mg to about 250 mg per day.

19. The method of any one of claims 10 - 14 wherein the therapeutically effective amount is from about 10 mg to about 100 mg per day.

20. The method of any one of claims 10 - 14 wherein the compound is a hydrochloride salt of

21. The method of any one of claims 10 - 14 further comprising administering a pharmaceutical composition comprising a therapeutically effective amount of the compound

or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipient or carrier.

22. The method of any one of claims 10 - 14 further comprising administering a pharmaceutical composition comprising a therapeutically effective amount of the compound

or a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable excipient or carrier, and a second active agent.

Assignees

• Sunovion Pharmaceuticals Inc

Inventors

• Hopkins Seth
• Koblan Kenneth
• Loebel Antony
• Ogirala Ajay

Classifications

• A61K31/435

  having six-membered rings with one nitrogen as the only ring hetero atom · CPC title

• C07D333/54

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring · CPC title

• C07D495/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61K31/381 Primary

  having five-membered rings · CPC title