Novel topiramate compositions and an escalating dosing strategy for treating obesity and related disorders

Abstract

The present invention is drawn to novel topiramate compositions as well as methods for treating obesity and related conditions, including conditions associated with and/or caused by obesity per se. The present invention also features a pharmaceutical composition that includes, e.g., topiramate alone or in combination with a sympathomimetic agent and a novel escalating dosing strategy for administering such compositions.

1 . A controlled release composition for treating obesity, diabetes or a related condition in a subject comprising:
 an effective amount of topiramate;   microcrystalline cellulose; and   methocellulose.   
     
     
         2 . The composition of  claim 1 , wherein the topiramate, the microcrystalline cellulose, and the methocellulose are present in a matrix core of a bead. 
     
     
         3 . The composition of  claim 2 , wherein the matrix core is coated with ethyl cellulose. 
     
     
         4 . The composition of  claim 3 , wherein the matrix core is further coated with polyvinyl pyrrolidone. 
     
     
         5 . The composition of  claim 4 , wherein the bead is encapsulated into a capsule. 
     
     
         6 . The composition of  claim 5 , wherein the capsule further comprises a sympathomimetic agent. 
     
     
         7 . The composition of  claim 6 , wherein the sympathomimetic agent is phentermine. 
     
     
         8 . The composition of  claim 7 , wherein the phentermine is coated onto a sugar sphere. 
     
     
         9 . The composition of  claim 7 , wherein the phentermine is coated onto the controlled release topiramate beads. 
     
     
         10 . The composition of  claim 7 , wherein the phentermine is an immediate release form. 
     
     
         11 . The composition of  claim 7 , wherein the phentermine is a controlled release form. 
     
     
         12 . The composition of  claim 6 , wherein the sympathomimetic agent is bupropion. 
     
     
         13 . The composition of  claim 12 , wherein the bupropion is coated onto a sugar sphere. 
     
     
         14 . The composition of  claim 12 , wherein the bupropion is coated onto the controlled release topiramate beads. 
     
     
         15 . The composition of  claim 12 , wherein the bupropion is an immediate release form. 
     
     
         16 . The composition of  claim 12 , wherein the bupropion is a controlled release form. 
     
     
         17 . The composition of  claim 7 , wherein the topiramate reduces phentermine exposure and reduces side effects associated with phentermine. 
     
     
         18 . The composition of  claim 12 , wherein the topiramate reduces bupropion exposure and reduces side effects associated with bupropion. 
     
     
         19 . A method for treating an individual for obesity or a related condition, the method comprising administering an effective amount of topiramate according to an escalating dosage strategy, wherein the topiramate is in a controlled-release form. 
     
     
         20 . The method according to  claim 19 , wherein the dosing strategy comprises:
 administering an initial daily dosage of topiramate to the individual for a specific period of time; and   incrementally increasing the dosage at various designated time points.   
     
     
         21 . The method according to  claim 20 , wherein the topiramate is administered at a dosage ranging from 20-100 mg/day. 
     
     
         22 . The method according to  claim 21 , wherein the initial dosage of topiramate is 23 mg/day. 
     
     
         23 . The method according to  claim 20 , further comprising administering an effective amount of a sympathomimetic agent. 
     
     
         24 . The method according to  claim 23 , wherein the sympathomimetic agent is phentermine. 
     
     
         25 . The method according to  claim 23 , wherein the sympathomimetic agent is bupropion. 
     
     
         26 . The method according to  claim 23 , wherein said sympathomimetic agent is in immediate release form. 
     
     
         27 . A method for treating obesity or a related condition in an individual by administering a non-toxic, effective amount of topiramate according to an escalating dosage strategy, the method comprising:
 administering an initial dose of topiramate for a first week at a dosage of 23 mg/day;   administering 46 mg/day of topiramate for a second one week administration after the first one week administration; and   administering 69 mg/day of topiramate for a third one week administration after the second one week administration; and   administering 92 mg/day of topiramate for a fourth one week administration after the third one week administration.   
     
     
         28 . The method according to  claim 27 , further comprising administering 3.75 mg/day of phentermine in the first one week administration. 
     
     
         29 . The method according to  claim 28 , further comprising administering 7.5 mg/day of phentermine in the second one week administration. 
     
     
         30 . The method according to  claim 29 , further comprising administering 11.25 mg/day of phentermine in the third one week administration. 
     
     
         31 . The method according to  claim 30 , further comprising administering 15.0 mg/day of phentermine in the fourth one week administration. 
     
     
         32 . A kit comprising topiramate and instructions providing a dosing strategy for administering topiramate to an individual for treating obesity or a related condition. 
     
     
         33 . The kit according to  claim 32 , wherein the dosing strategy provide a dosing strategy which includes administering a lower daily dosage of topiramate for a specific period of time and then incrementally increasing the dosage at various designated time points. 
     
     
         34 . The kit according to  claim 32 , further comprising:
 a sympathomimetic agent;   instructions providing a dosing strategy for administering the sympathomimetic agent in combination with the topiramate.   
     
     
         35 . The kit according to  claim 34 , wherein the topiramate and sympathomimetic agent are provided in a titration card, wherein the card provides dosages for four weeks. 
     
     
         36 . The kit according to  claim 35 , wherein the dosages increase each week.