Combinations comprising positive allosteric modulators or orthosteric agonists of metabotropic glutamatergic receptor subtype 2 and their use

Abstract

The present invention relates to combinations comprising a positive allosteric modulator (“PAM”) of metabotropic glutamatergic receptor subtype 2 (“mGluR2”) or a pharmaceutically acceptable salt or a solvate thereof, or an orthosteric agonist of metabotropic glutamatergic receptor subtype 2 compound or a pharmaceutically acceptable salt or a solvate thereof, and a synaptic vesicle protein 2A (“SV2A”) ligand.

1 - 21 . (canceled) 
     
     
         22 . A method for treating epilepsy comprising administering to a patient in need thereof:
 (a) a synaptic vesicle protein 2A (“SV2A”) ligand; and   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein the SV2A ligand and Compound 2a or the pharmaceutically acceptable salt thereof are administered in amounts that are therapeutically effective together, and 
         wherein the SV2A ligand and Compound 2a or the pharmaceutically acceptable salt thereof are administered together in a single dosage form or in separate dosage forms. 
       
     
     
         23 . The method of  claim 22 , wherein the SV2A ligand and a free base of Compound 2a are administered. 
     
     
         24 . The method of  claim 22 , wherein one or both of the SV2A and Compound 2a or the pharmaceutically acceptable salt thereof is in a non-effective dosage. 
     
     
         25 . The method of  claim 22 , wherein the SV2A ligand is selected from the group consisting of levetiracetam, brivaracetam, and seletracetam. 
     
     
         26 . The method of  claim 25 , wherein the SV2A ligand is levetiracetam or brivaracetam. 
     
     
         27 . The method of  claim 26 , wherein the SV2A ligand is levetiracetam. 
     
     
         28 . The method of  claim 26 , wherein the SV2A ligand is brivaracetam. 
     
     
         29 . The method of  claim 22 , wherein the SV2A ligand and Compound 2a or the pharmaceutically acceptable salt thereof are administered in separate dosage forms. 
     
     
         30 . The method of  claim 29 , wherein the separate dosage forms comprise:
 (i) a first dosage form comprising the SV2A ligand, and at least one pharmaceutically acceptable excipient; and   (ii) a second dosage form comprising Compound 2a or the pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.   
     
     
         31 . The method of  claim 30 , wherein the first dosage form and the second dosage form are administered sequentially or simultaneously. 
     
     
         32 . The method of  claim 31 , wherein the first dosage form and the second dosage form are administered sequentially. 
     
     
         33 . The method of  claim 31 , wherein the first dosage form and the second dosage form are administered simultaneously. 
     
     
         34 . The method of  claim 22 , wherein the SV2A ligand and Compound 2 or the pharmaceutically acceptable salt thereof are administered together in a single dosage form. 
     
     
         35 . The method of  claim 22 , wherein the SV2A ligand and Compound 2a or the pharmaceutically acceptable salt thereof are orally administered. 
     
     
         36 . The method of  claim 34 , wherein the single dosage form is an injectable solution or suspension. 
     
     
         37 . The method of  claim 30 , wherein at least one of the first dosage form and the second dosage form is an injectable solution or suspension. 
     
     
         38 . The method of  claim 22 , wherein the single dosage form or the separate dosage forms are part of a kit. 
     
     
         39 . The method of  claim 22 , wherein the epilepsy is focal onset seizures. 
     
     
         40 . The method of  claim 22 , wherein the epilepsy is myoclonic seizures. 
     
     
         41 . The method of  claim 22 , wherein the epilepsy is primary generalized tonic-clonic seizures. 
     
     
         42 . The method of  claim 22 , wherein the epilepsy is treatment resistant epilepsy.