Ganaxolone for use in treatment of status epilepticus

Abstract

This invention relates to methods for treating status epilepticus by administering to the subject in need thereof an intravenous bolus of ganaxolone and a continuous intravenous infusion of a neurosteroid. The method provides SE suppression and continued suppression of SE.

1 - 54 . (canceled) 
     
     
         55 . A method of treating status epilepticus (SE), comprising administering to a subject in need thereof an effective amount of ganaxolone, wherein the subject in need thereof weighs at least 40 kg and the effective amount is administered as an intravenous bolus plus continuous infusion, wherein:
 a) the intravenous bolus comprises about 20 mg to about 40 mg of ganaxolone and is administered over a period of about 1 minute to about 5 minutes;   b) the continuous infusion is administered for a treatment period of about 24 to about 36 hours, is initiated periprocedurally with the intravenous bolus, and comprises i) initially infusing about 70 to about 90 mg ganaxolone per hour into the subject, ii) about 2 hours after initiating the continuous infusion, decreasing the amount of ganaxolone infused per hour by about 50%, and iii) about 10 hours to about 14 hours after initiating the continuous infusion, further decreasing the amount of ganaxolone infused per hour by about 75% relative to the amount infused in b)i); and   c) following the treatment period, tapering the amount of ganaxolone infused into the subject to discontinue administration of intravenous ganaxolone.   
     
     
         56 . The method of  claim 55 , wherein the intravenous bolus comprises about 30 mg of ganaxolone. 
     
     
         57 . The method of  claim 56 , wherein the intravenous bolus is administered over about 3 minutes. 
     
     
         58 . The method of  claim 55 , wherein the continuous infusion in b)i) comprises about 80 mg ganaxolone per hour. 
     
     
         59 . The method of  claim 55 , wherein the intravenous bolus comprises about 30 mg of ganaxolone and is administered over about 3 minutes, and the continuous infusion comprises infusing about 80 mg ganaxolone per hour into the subject for about 2 hours, ii) then decreasing the amount of ganaxolone infused to about 40 mg per hour for about 10 hours, and iii) then further decreasing the amount of ganaxolone infused to about 20 mg per hour for at least about 12 hours through the end of the treatment period. 
     
     
         60 . The method of  claim 59 , wherein the continuous infusion of 20 mg ganaxolone per hour is for a period of at least about 12 hours, and optionally is followed by infusion of up to 45 mg ganaxolone per hour. 
     
     
         61 . The method of  claim 55 , wherein the tapering comprises reducing the amount of ganaxolone infused into the subject by about one third every four hours. 
     
     
         62 . The method of  claim 59 , wherein the tapering comprises reducing the amount of ganaxolone infused into the subject by about one third every four hours. 
     
     
         63 . The method of  claim 55 , further comprising orally administering ganaxolone to the subject in need thereof following the continuous infusion. 
     
     
         64 . The method of  claim 55 , wherein the ganaxolone is administered as an intravenous formulation comprising ganaxolone and sulfobutyl ether p-cyclodextrin. 
     
     
         65 . The method of  claim 59 , wherein the ganaxolone is administered as an intravenous formulation comprising ganaxolone and sulfobutyl ether β-cyclodextrin. 
     
     
         66 . A method of treating status epilepticus (SE), comprising administering to a subject in need thereof an effective amount of ganaxolone, wherein the subject in need thereof weighs less than 40 kg and the effective amount is administered as an intravenous bolus plus continuous infusion, wherein:
 a) the intravenous bolus comprises about 0.1 mg/kg to about 0.9 mg/kg ganaxolone and is administered over a period of about 1 minute to about 5 minutes;   b) the continuous infusion is administered for a treatment period of about 24 to about 36 hours, is initiated periprocedurally with the intravenous bolus, and comprises i) initially infusing about 0.8 mg/kg/hour to about 2 mg/kg/hour ganaxolone into the subject, ii) about 2 hours after initiating the continuous infusion, decreasing the amount of ganaxolone infused per hour by about 50%, and iii) about 10 hours to about 14 hours after initiating the continuous infusion, further decreasing the amount of ganaxolone infused per hour by about 75% relative to the amount infused in b)i); and   c) following the treatment period, tapering the amount of ganaxolone infused into the subject to discontinue administration of intravenous ganaxolone.   
     
     
         67 . The method of  claim 66 , wherein the intravenous bolus comprises about 0.75 mg/kg ganaxolone. 
     
     
         68 . The method of  claim 66 , wherein the intravenous bolus is administered over about 3 minutes. 
     
     
         69 . The method of  claim 66 , wherein the continuous infusion in b)i) comprises about 2 mg/kg/hour ganaxolone. 
     
     
         70 . The method of  claim 66 , wherein the intravenous bolus comprises about 0.75 mg/kg ganaxolone and is administered over about 3 minutes, and the continuous infusion comprises infusing about 2 mg/kg/hour ganaxolone into the subject for about 2 hours, and ii) then decreasing the amount of ganaxolone infused to about 1 mg/kg/hour for about 10 hours. 
     
     
         71 . The method of  claim 66 , wherein the tapering comprises reducing the amount of ganaxolone infused into the subject by about one third every four hours. 
     
     
         72 . The method of  claim 71 , wherein the tapering comprises reducing the amount of ganaxolone infused into the subject by about one third every four hours. 
     
     
         73 . The method of  claim 66 , further comprising orally administering ganaxolone to the subject in need thereof following the continuous infusion. 
     
     
         74 . The method of  claim 66 , wherein the ganaxolone is administered as an intravenous formulation comprising ganaxolone and sulfobutyl ether β-cyclodextrin. 
     
     
         75 . The method of  claim 71 , wherein the ganaxolone is administered as an intravenous formulation comprising ganaxolone and sulfobutyl ether β-cyclodextrin.