TH1901004574A - Hemisulfate nucleotide salt for the treatment of hepatitis C virus - Google Patents

Abstract

DEPCT63 Hemisulfate salt with structure: (chemical formula) for the treatment of hepatitis C infected hosts and its pharmaceutical composition and dosage forms, including its solid dosage forms [Figure 24].

Claims (77)

1. DEPCT63 1. Compounds with formula: (chemical formula) 2. The dosage form uses a solid containing (chemical formula) that provides a minimum steady-state plasma concentration (C24,ss) of approximately 2060 ng/mL of the metabolite (chemical formula). 3. The solid dosage form of claim 2, wherein the minimum concentration before the next dose at steady state in plasma (C24,ss) is approximately 2050 ng/mL. 4. The solid dosage form of claim 2, wherein the minimum concentration before the next dose at steady state in plasma (C24,ss) is approximately 2045 ng/mL. 5. The solid dosage form of claim 2, wherein the minimum concentration before the next dose at steady state in plasma (C24,ss) is approximately 2030 ng/mL. 6. The solid dosage form of claim 2, wherein the minimum concentration before the next dose at steady state in plasma (C24,ss) is approximately 2025 ng/mL. 7. A solid dosage form of any one of claim 26, wherein the area under the curve of the metabolite (chemical formula) is approximately between 1,500 ng*hr/mL and 3,000 ng*hr/mL. 8. The solid dosage form of claim 7, wherein the area under the curve is approximately between 1,800 ng*h/mL and 3,000 ng*h/mL. 9. The solid dosage form of claim 7, wherein the area under the curve is approximately between 2,100 ng*h/mL and 3,000 ng*h/mL. 10. The solid dosage form of claim 7, wherein the area under the curve is approximately between 2,400 ng*h/mL and 3,000 ng*h/mL. 11. The solid dosage form of claim 7, wherein the area under the curve is approximately between 2,700 ng*h/mL and 3,000 ng*h/mL. 12. The solid dosage form of claim 7, wherein the area under the curve is approximately between 2,000 ng*h/mL and 2,200 ng*h/mL. 13. Pharmaceutical composition comprising the effective amount of the compounds having the formula (chemical formula) in a pharmaceutically acceptable carrier. 14. The pharmaceutical composition of claim 13, in a solid dosage form delivering approximately 300 mg of the compound. 15. The pharmaceutical composition of claim 13, in a solid dosage form delivering approximately 400 mg of the compound. 16. The pharmaceutical composition of claim 13, in a solid dosage form delivering approximately 500 mg of the compound. 17. The pharmaceutical composition of claim 13, in a solid dosage form delivering approximately 600 mg of the compound. 18. The pharmaceutical composition of claim 13, in a solid dosage form delivering approximately 700 mg of the compound. 19. The pharmaceutical composition of claim 13, in a solid dosage form delivering approximately 800 mg of the compound. 20. The pharmaceutical composition of any one of the claims in claim 1319, wherein the dosage form uses a solid to provide a minimum steady-state plasma concentration (C24,ss) of the metabolite (chemical formula) between approximately 2060 ng/mL. 21. The pharmaceutical composition of claim 20, wherein the minimum steady-state plasma concentration of the solid (C24,ss) before the next dose is approximately 2050 ng/mL. 22. The pharmaceutical composition of claim 20, wherein the minimum steady state plasma concentration of the solid (C24,ss) before the next dose is approximately 2045 ng/mL. 23. The pharmaceutical composition of claim 20, wherein the minimum steady-state plasma concentration before the next dose of the solid (C24,ss) is approximately 2030 ng/mL. 24. The pharmaceutical composition of claim 20, wherein the minimum steady state plasma concentration of the solid (C24,ss) is approximately 2025 ng/mL. 25. The pharmaceutical composition of claim 17, wherein the solid dosage form provides a minimum steady-state plasma concentration (C24,ss) of the metabolite (chemical formula) between approximately 2060 ng/mL. 26. The pharmaceutical composition of claim 25, wherein the minimum steady state plasma concentration (C24,ss) before the next dose is approximately 4060 ng/mL. 27. The pharmaceutical composition of any one of claims 1326, wherein the pharmaceutically acceptable carrier is suitable for oral delivery. 28. The pharmaceutical composition of claim 27, wherein the pharmaceutically acceptable carrier is in the form of tablets. 29. Crystal form of the compound (chemical formula) where the compound contains less than 0.5% impurities when stored under ambient conditions for at least six months. 30. The crystal form of claim 29, wherein the crystal form is kept at approximately 0 and 40 degrees Celsius. 31. The crystal form of claim 29, wherein the crystal form is stored at a relative humidity of approximately 3080%. 32. A method for treating hepatitis C infection or conditions resulting from hepatitis C infection, in persons requiring it, comprising providing an effective amount of (the chemical formulation) in a pharmaceutically acceptable carrier. 33. The method of claim 32, wherein the compound is administered orally. 34. The method of claim 32, wherein the compound is delivered by controlled release. 35. The method of claim 32, wherein the conditions resulting from hepatitis C infection result in positive antibody and positive antigen, chronic viral hepatitis, liver cancer resulting from advanced hepatitis C, cirrhosis, or fatigue. 36. The method of any one of the claims in claim 3235, wherein at least 300 mg of the compound is given. 37. The method of any one of the claims in claim 3235, wherein at least 400 mg of the compound is given. 38. The method of any one of the claims in claim 3235, wherein at least 500 mg of the compound is given. 39. The method of any one of the claims in claim 3235, wherein at least 600 mg of the compound is given. 40. The method of any one of the claims in claim 3235, wherein at least 700 mg of the compound is given. 41. The method of any one of the claims in claim 3235, wherein at least 800 mg of the compound is given. 42. A method of any one of claims 3235, wherein the compound is administered for up to 12 weeks. 43. A method of any one of the claims in claim 3235, wherein the compound is administered for up to 8 weeks. 44. A method of any one of the claims in claim 3235, wherein the compound is administered for up to 6 weeks. 45. The method of any one of the claims in claim 3235, wherein the compound is administered for at least 6 weeks. 46. A method of any one of the claims in claim 3235, wherein the compound is administered for at least 8 weeks. 47. The method of any one of the claims in claim 3235, wherein the compound is administered for at least 12 weeks. 48. A method of any one of the claims in claim 4247, wherein the compound is given once daily. 49. A method of any one of the claims in claim 4247, wherein the compound is given every other day. 50. The method of any one of the claims in claim 3249, further comprising administering the compound in combination with another anti-HCV agent. 51. The method of claim 50, wherein the additional anti-HCV agent is selected from a group consisting of a protease inhibitor, an NS5A inhibitor, another NS5A polymerase inhibitor, a non-substrate inhibitor, interferon alpha 2a, ribavirin, a helicase inhibitor, an antisense oligodeoxynucleotide, an aptamer, a nuclease-resistant ribosome, an iRNA, an antibody to HCV, a partial antibody to HCV, and an antibody to HCV domain. 52. The method of claim 51, wherein the protease inhibitor is selected from the group consisting of telaprevir, boceprevir, simeprevir, and paritaprevir. 53. The method of claim 32, wherein the hepatitis C virus is of genotype 1a, 1b, 2a, 2b, 3a, 4a, 4d, 5a, or 6. 54. The method of claim 53, wherein the hepatitis C virus is of genotype 1a or 1b. 55. The method of claim 53, wherein the hepatitis C virus is of genotype 2a or 2b. 56. The method of claim 53, wherein the hepatitis C virus is genotype 3a. 57. The method of claim 53, wherein the hepatitis C virus is of genotype 4a or 4b. 58. The method of claim 53, wherein the hepatitis C virus is of genotype 5a. 59. A method of any one of the claims in claim 3258, wherein the subject is a human being. 60. Compounds having a formula (chemical formula) of choice in pharmaceutically acceptable carriers, for use in the treatment of hepatitis C infection or conditions resulting from hepatitis C infection, in those who need it. 61. The compound of claim 60, wherein the compound is administered orally. 62. The compound of claim 60, wherein the compound is delivered by controlled release. 63. The compound of claim 60, wherein the condition resulting from hepatitis C infection results in antibody-positive and antigen-positive conditions, chronic viral hepatitis, liver cancer resulting from advanced hepatitis C, cirrhosis, or fatigue. 64. The compound of any one of the claims in claim 6063, wherein at least 300 mg of the compound is given. 65. The compound of any one of the claims in claim 6063, wherein at least 400 mg of the compound is given. 66. The compound of any one of the claims in claim 6063, wherein at least 500 mg of the compound is given. 67. The compound of any one of the claims in claim 6063, wherein at least 600 mg of the compound is given. 68. Any compound of any one of the claims in claim 6067, further comprising the compound in combination with another anti-HCV agent. 69. The compound of claim 68, wherein the additional anti-HCV agent is selected from a group consisting of a protease inhibitor, an NS5A inhibitor, another NS5A polymerase inhibitor, a non-substrate inhibitor, interferon alpha 2a, ribavirin, a helicase inhibitor, an antisense oligodeoxynucleotide, an aptamer, a nuclease-resistant ribosome, an iRNA, an antibody to HCV, a partial antibody to HCV, and an antibody to HCV domain. 70. Use of the compound having the formula (chemical formula) selectively in pharmaceutically acceptable carriers, in the preparation of drugs for the treatment of hepatitis C infection or conditions resulting from hepatitis C infection, in those who need it. 71. The use of claim 70, wherein the compound is administered orally. 72. The use of claim 70, wherein the compound is delivered by controlled release. 73. An application of claim 70, wherein the condition resulting from hepatitis C infection results in a positive antibody and a positive antigen, chronic viral hepatitis, liver cancer resulting from advanced hepatitis C, cirrhosis, or fatigue. 74. Use of any one of the claims in claim 7073, wherein at least 300 mg of the compound is given. 75. Use of any one of the claims in claim 7073, wherein at least 400 mg of the compound is given. 76. Use of any one of the claims in claim 7073, wherein at least 500 mg of the compound is given. 77. Use of any one of the claims in claim 7073, wherein at least 600 mg of the compound is given.