Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
Provided herein are low impurity compositions comprising a compound represented by Formula (I): which are useful in the treatment of disorders related to the activity of the c-KIT and PDGFRα kinases, and oncogenic forms thereof.
1. A method of treating gastrointestinal stromal tumors in a patient in need thereof, comprising administering to the patient, once daily, one or more pharmaceutically acceptable tablets for orally delivering a compound represented by Formula (I):
wherein each pharmaceutically acceptable tablet comprises:
a solid dispersion comprising:
(a) 50 mg of the compound wherein the compound is present in amorphous form; and
(b) hydroxypropyl methyl cellulose acetate succinate; and
aniline in an amount equal to or less than about 5% by weight based on the total weight of the pharmaceutically acceptable tablet.
2. The method of claim 1 , comprising aniline in an amount equal to or less than about 3% by weight based on the total weight of the pharmaceutically acceptable tablet.
3. The method of claim 1 , comprising aniline in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet.
4. The method of claim 1 , comprising aniline in an amount equal to or less than about 1% by weight based on the total weight of the pharmaceutically acceptable tablet.
5. The method of claim 1 , comprising aniline in an amount equal to or less than about 0.5% by weight based on the total weight of the pharmaceutically acceptable tablet.
6. The method of claim 1 , comprising aniline in an amount equal to or less than about 0.3% by weight based on the total weight of the pharmaceutically acceptable tablet.
7. The method of claim 1 , wherein each pharmaceutically acceptable tablet comprises:
(i) aniline in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet;
(ii) a compound represented by Formula (II):
in an amount equal to or less than about 0.40% by weight based on the total weight of the pharmaceutically acceptable tablet; and
(iii) diphenyl urea in an amount equal to or less than about 0.2% by weight based on the total weight of the pharmaceutically acceptable tablet.
8. The method of claim 1 , wherein each pharmaceutically acceptable tablet comprises:
(i) aniline in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet;
(ii) a compound represented by Formula (II):
in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet; and
(iii) diphenyl urea in an amount equal to or less than about 0.2% by weight based on the total weight of the pharmaceutically acceptable tablet.
9. A method of treating gastrointestinal stromal tumors in a patient in need thereof, comprising administering to the patient, once daily, one or more pharmaceutically acceptable tablets for oral delivery, wherein each pharmaceutically acceptable tablet comprises:
a solid dispersion comprising:
(a) a compound represented by Formula (I):
wherein the compound is present in amorphous form; and
(b) hydroxypropyl methyl cellulose acetate succinate; and
aniline in an amount equal to or less than about 5% by weight based on the total weight of the pharmaceutically acceptable tablet.
10. The method of claim 9 , comprising aniline in an amount equal to or less than about 3% by weight based on the total weight of the pharmaceutically acceptable tablet.
11. The method of claim 9 , comprising aniline in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet.
12. The method of claim 9 , comprising aniline in an amount equal to or less than about 1% by weight based on the total weight of the pharmaceutically acceptable tablet.
13. The method of claim 9 , comprising aniline in an amount equal to or less than about 0.5% by weight based on the total weight of the pharmaceutically acceptable tablet.
14. The method of claim 9 , comprising aniline in an amount equal to or less than about 0.3% by weight based on the total weight of the pharmaceutically acceptable tablet.
15. The method of claim 9 , wherein each pharmaceutically acceptable tablet comprises:
(i) aniline in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet;
(ii) a compound represented by Formula (II):
in an amount equal to or less than about 0.40% by weight based on the total weight of the pharmaceutically acceptable tablet; and
(iii) diphenyl urea in an amount equal to or less than about 0.2% by weight based on the total weight of the pharmaceutically acceptable tablet.
16. The method of claim 9 , wherein each pharmaceutically acceptable tablet comprises:
(i) aniline in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet;
(ii) a compound represented by Formula (II):
in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet; and
(iii) diphenyl urea in an amount equal to or less than about 0.2% by weight based on the total weight of the pharmaceutically acceptable tablet.
17. A method of treating gastrointestinal stromal tumors in a patient in need thereof, comprising administering to the patient, once daily, one or more pharmaceutically acceptable tablets for orally delivering a compound represented by Formula (I):
wherein each pharmaceutically acceptable tablet comprises:
(i) a solid dispersion and one or more pharmaceutically acceptable carriers, wherein the solid dispersion comprises:
(a) 50 mg of the compound wherein the compound is present in amorphous form; and
(b) hydroxypropyl methyl cellulose acetate succinate;
(ii) aniline in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet;
(iii) a compound represented by Formula (II):
in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet; and
(iv) diphenyl urea in an amount equal to or less than about 0.2% by weight based on the total weight of the pharmaceutically acceptable tablet.
18. The method of claim 17 , wherein each pharmaceutically acceptable tablet comprises:
(ii) aniline in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet;
(iii) a compound represented by Formula (II):
in an amount equal to or less than about 0.40% by weight based on the total weight of the pharmaceutically acceptable tablet; and
(iv) diphenyl urea in an amount equal to or less than about 0.2% by weight based on the total weight of the pharmaceutically acceptable tablet.
19. A method of treating gastrointestinal stromal tumors in a patient in need thereof, comprising administering to the patient, once daily, one or more pharmaceutically acceptable tablets for oral delivery, wherein each pharmaceutically acceptable tablet comprises:
(i) a solid dispersion and one or more pharmaceutically acceptable carriers, wherein the solid dispersion comprises:
(a) an amorphous form of a compound represented by Formula (I):
and
(b) hydroxypropyl methyl cellulose acetate succinate;
(ii) aniline in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet;
(iii) a compound represented by Formula (II):
in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet; and
(iv) diphenyl urea in an amount equal to or less than about 0.2% by weight based on the total weight of the pharmaceutically acceptable tablet.
20. The method of claim 19 , wherein each pharmaceutically acceptable tablet comprises:
(ii) aniline in an amount equal to or less than about 2% by weight based on the total weight of the pharmaceutically acceptable tablet;
(iii) a compound represented by Formula (II):
in an amount equal to or less than about 0.40% by weight based on the total weight of the pharmaceutically acceptable tablet; and
(iv) diphenyl urea in an amount equal to or less than about 0.2% by weight based on the total weight of the pharmaceutically acceptable tablet.