Solid state forms of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide and uses thereof
The present disclosure relates to: a) solid state forms of hydrobromide salts of Compound 1; b) pharmaceutical compositions comprising one or more solid state forms of hydrobromide salts of Compound 1, and, optionally, a pharmaceutically acceptable carrier; c) methods of treating tumors or cancers by administering one or more solid state forms of hydrobromide salts of Compound 1 to a subject in need thereof; and d) methods for the preparation of solid state forms of Compound 1.
1. Amorphous form of a hydrobromide salt of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide of Formula (I)
2. The amorphous form of claim 1 , wherein the amorphous form is characterized by an XRPD pattern substantially as shown in FIG. 31 .
3. The amorphous form of claim 1 , wherein the amorphous form is substantially free of polymorphic forms.
4. The amorphous form of claim 1 , wherein the amorphous form has a polymorphic purity of at least 90%.
5. The amorphous form of claim 1 , wherein the amorphous form has a polymorphic purity of at least 99%.
6. The amorphous form of claim 1 , wherein the amorphous form has one or more of a D[V, 0.10] particle size between 0.5 μm and 15 μm, D[V,0.50] particle size between 2 μm and 30 μm, D[V,0.90] particle size between 8 μm and about 600 μm, or a D[4,3] particle size of 5 μm to 200 μm.
7. A pharmaceutical composition comprising the amorphous form of a hydrobromide salt of (S)-2-4(S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide of Formula (I)
of claim 1 and a pharmaceutically acceptable carrier.
8. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition is a tablet.
9. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition comprises 25 mg to 400 mg of the hydrobromide salt of (S)-24(S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide.
10. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition comprises 50 mg of the hydrobromide salt of (S)-2-(((S)-6,8-di fluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide.
11. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition comprises 100 mg of the hydrobromide salt of (S) (((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl (neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide.
12. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition comprises 150 mg of the hydrobromide salt of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide.
13. A method of treating desmoid tumors comprising administering to a subject in need of such treatment a pharmaceutical composition of claim 7 .
14. The method of claim 13 , wherein the subject is administered 50 mg to 500 mg of the hydrobromide salt of (S)-2-(((S)-6,8-di fluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentyl amino) propan-2-yl)-1H-imidazol-4-yl)pentanamide daily.
15. The method of claim 13 , wherein the subject is administered 100 mg to 400 mg of the hydrobromide salt of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide daily.
16. The method of claim 13 , wherein the subject is administered 300 mg of the hydrobromide salt of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide daily.
17. The method of claim 13 , wherein the subject is administered 200 mg of the hydrobromide salt of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide daily.
18. The method of claim 13 , wherein a total daily dose is provided as two separate doses.
19. The method of claim 18 , wherein the total daily dose is provided as two separate doses of 150 mg.
20. The method of claim 18 , wherein the total daily dose is provided as two separate doses of 100 mg.