Claims for Patent: 11,578,062

Summary for Patent: 11,578,062

Title:	Solid forms of (R)-1(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide
Abstract:	The present invention relates to solid forms of (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide (Compound 1) in substantially crystalline form (Form A) or amorphous form, pharmaceutical compositions thereof, and methods of treatment therewith.
Inventor(s):	Ali Keshavarz-Shokri, Beili Zhang, Tim Edward Alcacio, Elaine Chungmin Lee, Yuegang Zhang, Mariusz Krawiec
Assignee:	Vertex Pharmaceuticals Inc
Application Number:	US17/104,903
Patent Claims:	1. A solid dispersion comprising substantially amorphous (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide (Compound 1) and a polymer, wherein the substantially amorphous Compound 1 comprises less than about 15% crystalline Compound 1. 2. The solid dispersion of claim 1, wherein the substantially amorphous Compound 1 comprises less than about 10% crystalline Compound 1. 3. The solid dispersion of claim 1, wherein the substantially amorphous Compound 1 comprises less than about 5% crystalline Compound 1. 4. The solid dispersion of claim 1, wherein the polymer is present in the solid dispersion in an amount of from 10% by weight to 80% by weight of the solid dispersion. 5. The solid dispersion of claim 1, wherein the polymer is selected from hydroxypropylmethylcellulose (HPMC) and hydroxypropylmethylcellulose acetate succinate (HPMCAS). 6. A pharmaceutical composition comprising a solid dispersion, wherein the solid dispersion comprises substantially amorphous (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide (Compound 1) and a polymer, wherein the substantially amorphous Compound 1 comprises less than about 15% crystalline Compound 1. 7. The pharmaceutical composition of claim 6, wherein the substantially amorphous Compound 1 in the solid dispersion comprises less than about 10% crystalline Compound 1. 8. The pharmaceutical composition of claim 6, wherein the substantially amorphous Compound 1 in the solid dispersion comprises less than about 5% crystalline Compound 1. 9. The pharmaceutical composition of claim 6, wherein the polymer of the solid dispersion is present in an amount of from 10% by weight to 80% by weight of the solid dispersion. 10. The pharmaceutical composition of claim 6, wherein the polymer of the solid dispersion is selected from hydroxypropylmethylcellulose (HPMC) and hydroxypropylmethylcellulose acetate succinate (HPMCAS). 11. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition further comprises an additional therapeutic agent selected from a mucolytic agent, a bronchodilator, an antibiotic, an anti-infective agent, an anti-inflammatory agent, a CFTR potentiator, and a nutritional agent. 12. The pharmaceutical composition of claim 11, wherein the additional therapeutic agent is N-(5-hydroxy-2,4-di-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide. 13. A method of treating cystic fibrosis comprising administering to a patient a pharmaceutical composition comprising a solid dispersion comprising substantially amorphous (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide (Compound 1) and a polymer, wherein the substantially amorphous Compound 1 comprises less than about 15% crystalline Compound 1. 14. The method of claim 13, wherein the substantially amorphous Compound 1 comprises less than about 10% crystalline Compound 1. 15. The method of claim 13, wherein the substantially amorphous Compound 1 comprises less than about 5% crystalline Compound 1. 16. The method of claim 13, wherein the polymer of the solid dispersion is present in an amount of from 10% by weight to 80% by weight of the solid dispersion. 17. The method of claim 13, wherein the polymer of the solid dispersion is selected from hydroxypropylmethylcellulose (HPMC) and hydroxypropylmethylcellulose acetate succinate (HPMCAS). 18. The method of claim 13, wherein the method further comprises administering an additional therapeutic agent selected from a mucolytic agent, a bronchodilator, an antibiotic, an anti-infective agent, an anti-inflammatory agent, a CFTR potentiator, and a nutritional agent. 19. The pharmaceutical composition of claim 18, wherein the additional therapeutic agent is N-(5-hydroxy-2,4-di-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide.