Formulations of an lsd1 inhibitor

Abstract

The present application relates to pharmaceutical formulations and dosage forms of a lysine specific demethylase-1 (LSD1) inhibitor, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, including methods of preparation thereof, which are useful in the treatment of LSD1 mediated diseases such as cancer.

1 . A pharmaceutical formulation in solid oral dosage form comprising:
 (a) an inhibitor of LSD1 which is Compound 1 di-tosylate salt of the formula:   
       
         
           
           
               
               
           
         
       
       or a solvate or hydrate thereof, and
 (b) an organic acid. 
 
     
     
         2 . The pharmaceutical formulation of  claim 1 , further comprising a diluent. 
     
     
         3 . The pharmaceutical formulation of  claim 1 , wherein the organic acid is fumaric acid or citric acid. 
     
     
         4 . The pharmaceutical formulation of  claim 3 , wherein the organic acid is fumaric acid. 
     
     
         5 . The pharmaceutical formulation of  claim 4 , comprising about 1 wt % to about 50 wt % of fumaric acid. 
     
     
         6 . The pharmaceutical formulation of  claim 4 , comprising about 1 wt % to about 15 wt % of fumaric acid. 
     
     
         7 . The pharmaceutical formulation of  claim 4 , comprising about 5 wt % to about 15 wt % of fumaric acid. 
     
     
         8 . The pharmaceutical formulation of  claim 4 , comprising about 9 wt % to about 11 wt % of fumaric acid. 
     
     
         9 . The pharmaceutical formulation of  claim 4 , comprising about 10 wt % of fumaric acid. 
     
     
         10 . The pharmaceutical formulation of  claim 1 , comprising about 1 wt % to about 5 wt % of the LSD1 inhibitor. 
     
     
         11 . The pharmaceutical formulation of  claim 1 , comprising about 2 wt % to about 4 wt % of the LSD1 inhibitor. 
     
     
         12 . The pharmaceutical formulation of  claim 1 , comprising about 3 wt % of the LSD1 inhibitor. 
     
     
         13 . The pharmaceutical formulation of  claim 2 , wherein the diluent is lactose or mannitol. 
     
     
         14 . The pharmaceutical formulation of  claim 13 , wherein the lactose is lactose monohydrate or lactose-316 Fast Flo®. 
     
     
         15 . The pharmaceutical formulation of  claim 14 , comprising about 80 wt % to about 97 wt % of lactose monohydrate. 
     
     
         16 . The pharmaceutical formulation of  claim 14 , comprising about 85 wt % to about 97 wt % of lactose monohydrate. 
     
     
         17 . The pharmaceutical formulation of  claim 1  further comprising a lubricant, glidant, or both. 
     
     
         18 . The pharmaceutical formulation of  claim 17 , wherein the lubricant is sodium stearyl fumarate or stearic acid. 
     
     
         19 . The pharmaceutical formulation of  claim 18 , wherein the lubricant is sodium stearyl fumarate. 
     
     
         20 . The pharmaceutical formulation of  claim 19 , comprising about 1 wt % to about 5 wt % of sodium stearyl fumarate. 
     
     
         21 . The pharmaceutical formulation of  claim 20 , comprising about 2 wt % of sodium stearyl fumarate. 
     
     
         22 . The pharmaceutical formulation of  claim 18 , wherein the lubricant is stearic acid. 
     
     
         23 . The pharmaceutical formulation of  claim 22 , comprising about 1 wt % to about 5 wt % of stearic acid. 
     
     
         24 . The pharmaceutical formulation of  claim 22 , comprising about 2 wt % of stearic acid. 
     
     
         25 . The pharmaceutical formulation of  claim 17 , wherein the glidant is colloidal silica. 
     
     
         26 . A pharmaceutical formulation comprising:
 (a) 1-{[4-(methoxymethyl)-4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid di-tosylate salt (Compound 1 di-tosylate salt), or a solvate or hydrate thereof;   (b) fumaric acid; and   (c) lactose or mannitol, or a solvate or hydrate thereof.   
     
     
         27 . (canceled) 
     
     
         28 . The pharmaceutical formulation of  claim 26  further comprising sodium stearyl fumarate. 
     
     
         29 . The pharmaceutical formulation of  claim 26  further comprising stearic acid. 
     
     
         30 .- 31 . (canceled) 
     
     
         32 . The pharmaceutical formulation of  claim 1 , further comprising a disintegrant. 
     
     
         33 . The pharmaceutical formulation of  claim 32 , wherein the disintegrant is croscarmellose sodium, sodium starch glycolate or crospovidone. 
     
     
         34 . The pharmaceutical formulation of  claim 1 , wherein the Compound 1 di-tosylate salt, or hydrate or solvate thereof, is in crystalline form. 
     
     
         35 . The pharmaceutical formulation of  claim 34 , wherein the crystalline form comprises Form I. 
     
     
         36 . The pharmaceutical formulation of  claim 34 , wherein the crystalline form comprises Form HI. 
     
     
         37 . The pharmaceutical formulation of  claim 1 , wherein the dosage form is a tablet or capsule. 
     
     
         38 .- 48 . (canceled)