METHODS FOR TREATING CHOLESTASIS
Provided herein are methods for treating cholestasis in a subject having a liver disease. The method includes administering to the subject an Apical Sodium-dependent Bile Acid Transporter (ASBTI). More specifically, the present invention relates to methods for treating cholestasis in a subject where the method includes administering an ASBTI to a subject at a dose of at least 10 μg/kg/day.
1 . A method for treating primary sclerosing cholangitis (PSC) in a subject comprising administering to the subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI), wherein the ASBTI is selected from the group consisting of maralixibat, or a pharmaceutically acceptable salt thereof, which is administered in an amount of from about 400 μg/kg/day to about 1400 μg/kg/day, and volixibat, or a pharmaceutically acceptable salt thereof, which is administered in an amount from about 4 mg/day to about 300 mg/day.
2 . (canceled)
3 . The method of claim 1 , wherein the ASBTI is maralixibat chloride.
4 . The method of claim 1 , wherein the ASBTI is volixibat, or a pharmaceutically acceptable salt thereof.
5 .- 17 . (canceled)
18 . The method of claim 1 , wherein the subject is a pediatric subject.
19 . The method of claim 1 , wherein the ASBTI is administered once daily (QD).
20 . The method of claim 1 , wherein the ASBTI is administered twice daily (BID).
21 . The method of claim 1 , wherein the ASBTI is maralixibat, or a pharmaceutically acceptable salt thereof, and the ASBTI is administered in an amount of from about 400 μg/kg/day to about 800 μg/kg/day.
22 . (canceled)
23 . The method of 22 claim 1 , wherein the administration of the ASBTI reduces a symptom or changes a disease-relevant laboratory measure of the PSC that is maintained for at least one year.
24 . The method of claim 23 , wherein the reduction in the symptom or a change in a disease-relevant laboratory measure comprises a reduction in sBA concentration, an increase in serum 7α-hydroxy-4-cholesten-3-one (7αC4) concentration, an increase in a ratio of serum 7αC4 concentration to serum bile acids (sBA) concentration (7αC4:sBA), a reduction in pruritus, an increase in a quality of life inventory score, an increase in a quality of life inventory score related to fatigue, an increase in growth, or a combination thereof.
25 . The method of claim 24 , wherein the reduction in the symptom or a change in a disease-relevant laboratory measure is determined relative to a baseline level.
26 .- 74 . (canceled)
75 . The method of claim 1 , wherein the subject is an adult.
76 . (canceled)
77 . (canceled)
78 . The method of claim 1 , wherein the ASBTI is volixibat, or a pharmaceutically acceptable salt thereof, and the ASBTI is administered in an amount of about 10 mg/day to about 200 mg/day.
79 .- 83 . (canceled)
84 . The method of claim 1 , wherein the administration of the ASBTI reduces severity of pruritus.
85 . The method of claim 84 , wherein an ITCHRO score of the subject is reduced by at least 40% relative to baseline by 14 weeks.
86 . The method of claim 85 , wherein the ITCHRO score of the subject is reduced by at least 60% relative to a baseline ITCHRO score of 4 or higher.
87 . The method of claim 1 , wherein the administration of the ASBTI results in a reduction in sBA concentration of at least 30% relative to baseline.
88 . (canceled)
89 . The method of claim 1 , wherein the administration of the ASBTI results in a reduction in total serum cholesterol concentration of at least 10 mg/dL.
90 .- 102 . (canceled)
103 . The method of claim 1 , where the administration of the ASBTI reduces one or more of inflammation, fibrosis and obstruction of large and medium sized intra- and extrahepatic ductuli.
104 . The method of claim 1 , where the administration of the ASBTI reduces fibrosis.
105 . The method of claim 78 , wherein the volixibat, or the pharmaceutically acceptable salt thereof, is administered BID at an amount of about 10 mg to about 80 mg per dose.