Pharmaceutical compositions for combination therapy

Abstract

This invention relates to novel pharmaceutical compositions comprising a therapeutically effective combination of a dopaminergic stabilizer known as Pridopidine, and an inhibitor of the vesicular monoamine transporter type 2 (VMAT) known as Tetrabenazine. The pharmaceutical compositions for use according to the invention are contemplated particularly useful for improving the symptomatic therapeutic effects, and for reducing the adverse effects, of Tetrabenazine in the treatment of movement disorders, and in particular movement disorders associated with Huntington's disease, Gilles de la Tourette's syndrome, or tardive dyskinesia.

1 . A method of treating a subject afflicted with a movement disorder comprising periodically administering to the subject an amount of Tetrabenazine or a pharmaceutically acceptable salt thereof, and an amount of Pridopidine or a pharmaceutically acceptable salt thereof. 
     
     
         2 . A method of treating a subject afflicted with obesity, an obesity associated disorder, or a cardiovascular side effect of Pridopidine comprising administering to the subject an amount of Pridopidine or a pharmaceutically acceptable salt thereof, and an amount of Tetrabenazine or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The method of  claim 1 , wherein the amounts when taken together are more effective to treat the subject than when each agent at the same amount is administered alone. 
     
     
         4 . The method of  claim 1 , wherein either the amount of Tetrabenazine or a pharmaceutically acceptable salt thereof when taken alone, and the amount of Pridopidine or a pharmaceutically acceptable salt thereof when taken alone, or each such amount when taken alone is not effective to treat the subject. 
     
     
         5 . A method of reducing or preventing one or more side effects of periodic administration of an amount of Tetrabenazine or a pharmaceutically acceptable salt thereof to a subject, comprising periodically administering to the subject an amount of Pridopidine or a pharmaceutically acceptable salt thereof. 
     
     
         6 . The method of  claim 5 , wherein the one or more side effects are selected from depression, suicidality, akathisia, restlessness, agitation, parkinsonism, sedation, somnolence, and dysphagia. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 5 , wherein the subject is afflicted with a movement disorder. 
     
     
         9 .- 12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the amount of Tetrabenazine or a pharmaceutically acceptable salt thereof is 0.05 mg/kg per day to 0.20 mg/kg per day. 
     
     
         14 . The method of  claim 1 , wherein the amount of Tetrabenazine or a pharmaceutically acceptable salt thereof is 5-100 mg/day. 
     
     
         15 . The method of  claim 14 , wherein the amount of Tetrabenazine or a pharmaceutically acceptable salt thereof is 12.5 mg/day, 25 mg/day, 37.5 mg/day, 50 mg/day, 75 mg/day, or 100 mg/day. 
     
     
         16 .- 18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein the amount of Pridopidine or a pharmaceutically acceptable salt thereof is 1.5 μmol/kg per day to 20 μmol/kg per day. 
     
     
         20 . The method of  claim 1 , wherein the amount of Pridopidine or a pharmaceutically acceptable salt thereof is 10-100 mg/day. 
     
     
         21 . The method of  claim 20 , wherein the amount of Pridopidine or a pharmaceutically acceptable salt thereof is 10 mg/day, 20 mg/day, 22.5 mg/day, 45 mg/day, or 90 mg/day. 
     
     
         22 . The method of  claim 1 , wherein the movement disorder is Huntington's disease, Tourette's syndrome, or tardive dyskinesia. 
     
     
         23 . The method of  claim 1 , wherein the amount of Tetrabenazine or a pharmaceutically acceptable salt thereof and the amount of Pridopidine or a pharmaceutically acceptable salt thereof is effective to alleviate a symptom of the movement disorder. 
     
     
         24 . The method of  claim 23 , wherein the symptom is chorea. 
     
     
         25 . The method of  claim 1 , wherein the subject is receiving Tetrabenazine therapy prior to initiating administration of Pridopidine or a pharmaceutically acceptable salt thereof. 
     
     
         26 . The method of  claim 1 , wherein the amount of Tetrabenazine or a pharmaceutically acceptable salt thereof and the amount of Pridopidine or a pharmaceutically acceptable salt thereof are administered simultaneously. 
     
     
         27 . The method of  claim 1 , wherein the subject is a human patient. 
     
     
         28 . A package comprising:
 a) a first pharmaceutical composition comprising an amount of Tetrabenazine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier;   b) a second pharmaceutical composition comprising and amount of Pridopidine or pharmaceutical acceptable salt thereof and a pharmaceutically acceptable carrier; and   c) instruction for use for the first and the second pharmaceutical compositions together to treat a subject afflicted a movement disorder.   
     
     
         29 .- 49 . (canceled)