Insulin glargine/lixisenatide fixed ratio formulation

Abstract

The present invention refers to a pharmaceutical composition comprising (a) lixisenatide or/and a pharmaceutically acceptable salt thereof, and (b) insulin glargine or/and a pharmaceutically acceptable salt thereof, wherein the compound (b) and compound (a) are present in a fixed ratio.

1 . A pharmaceutical composition comprising
 (a) lixisenatide or/and a pharmaceutically acceptable salt thereof, and   (b) insulin glargine or/and a pharmaceutically acceptable salt thereof,   wherein the compound (b) and compound (a) are present in a ratio of about 1.6 to about 2.4 U of compound (b) per 1 μg of compound (a).   
     
     
         2 . The composition of  claim 1 , wherein the concentration of compound (a) is in the range of 40-60 μg/ml, and wherein the concentration of compound (b) is in the range of 64-144 U/ml. 
     
     
         3 . The composition of  claim 2 , with the proviso that the concentration of compound (a) is not a concentration selected from 55.56 μg/mL, 51.28 μg/mL, 47.62 μg/mL, 44.44 μg/mL, and 41.67 μg/mL. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the compound (b) and compound (a) are present in a ratio of about 2 U of compound (b) per μg of compound (a). 
     
     
         5 . The pharmaceutical composition of  claim 1 , for use in the treatment of diabetes mellitus type 1 or/and 2. 
     
     
         6 . The pharmaceutical composition for use of  claim 5 , by administration of a dose of 0.25 to 1.5 U/kg body weight insulin glargine. 
     
     
         7 . The pharmaceutical composition for use of  claim 5 , by administration of a dose of 0.05 to 0.5 μg/kg body weight lixisenatide. 
     
     
         8 . The pharmaceutical composition for use of  claim 5 , wherein the subject to be treated is obese. 
     
     
         9 . The pharmaceutical composition for use of  claim 5 , wherein diabetes mellitus type 2 is not adequately controlled with metformin alone. 
     
     
         10 . The pharmaceutical composition for use of  claim 5 , wherein the subject to be treated has a HbA1c value in the range of at least 7%, at least 8% or at least 9% at the onset of treatment with the composition. 
     
     
         11 . The pharmaceutical composition for use of  claim 5 , wherein the subject to be treated has a fasting plasma glucose concentration of at least 7 mmol/L, at least 8 mmol/L, at least 9 mmol/L, at least 10 mmol/L, or at least 11 mmol/L at the onset of treatment with the composition. 
     
     
         12 . The pharmaceutical composition for use of  claim 5 , wherein the patient to be treated has a self-monitored plasma glucose concentration of at least 8 mmol/L, at least 9 mmol/L, at least 10 mmol/L, or at least 11 mmol/L at the onset of treatment with the composition. 
     
     
         13 . The pharmaceutical composition for use of  claim 5 , wherein the subject to be treated has a 2-hour postprandial plasma glucose of at least 12 mmol/L, at least 13 mmol/L, at least 14 mmol/L, at least 15 mmol/L, at least 16 mmol/L, or at least 17 mmol/L at the onset of treatment with the composition. 
     
     
         14 . The pharmaceutical composition for use of  claim 5 , wherein the patient to be treated has a 2-hour postprandial plasma glucose excursion of at least 5 mmol/L, at least 5.5 mmol/L, at least 6 mmol/L, at least 6.5 mmol/L, or at least 7 mmol/L at the onset of treatment with the composition. 
     
     
         15 . The pharmaceutical composition for use of  claim 5 , wherein the patient to be treated does not receive a GLP-1 receptor agonist or/and an insulin. 
     
     
         16 . The pharmaceutical composition for use of  claim 5 , wherein the composition is administered parenterally. 
     
     
         17 . The pharmaceutical composition for use of  claim 5 , wherein the subject to be treated is at least 50 years old. 
     
     
         18 . The pharmaceutical composition for use of  claim 5 , wherein the subject to be treated has a body mass index of at least 30 kg/m 2 , at least 31 kg/m 2 , at least 32 kg/m 2  or at least 33 kg/m 2 . 
     
     
         19 . The pharmaceutical composition for use of  claim 5 , wherein a treatment with at least 1.5 g/day of metformin does not adequately control the diabetes mellitus type 2. 
     
     
         20 . The pharmaceutical composition of  claim 1 , with the proviso that the composition is not an on-site mixed composition. 
     
     
         21 . The pharmaceutical composition of  claim 1 , which is provided within a container. 
     
     
         22 . Use of a composition of
 (a) lixisenatide or/and a pharmaceutically acceptable salt thereof, and   (b) insulin glargine or/and a pharmaceutically acceptable salt thereof,   for the preparation of a composition for the treatment of diabetes mellitus type 1 or/and 2,   wherein the compound (b) and compound (a) are present in the composition in a ratio of about 1.6 to about 2.4 U of compound (b) per μg of compound (a).   
     
     
         23 . The use of  claim 22 , wherein the compound (b) and compound (a) are present in the composition in a ratio of about 2 U of compound (b) per μg of compound (a). 
     
     
         24 . The use of  claim 22 , wherein the patient to be treated:
 is obese;   has diabetes mellitus type 2 not adequately controlled with metformin alone;   has a HbA1c value in the range of at least 7%, at least 8% or at least 9% at the onset of treatment with the composition;   has a fasting plasma glucose concentration of at least 7 mmol/L, at least 8 mmol/L, at least 9 mmol/L, at least 10 mmol/L, or at least 11 mmol/L at the onset of treatment with the composition;   has a self-monitored plasma glucose concentration of at least 8 mmol/L, at least 9 mmol/L, at least 10 mmol/L, or at least 11 mmol/L at the onset of treatment with the composition;   has a 2-hour postprandial plasma glucose of at least 12 mmol/L at least 13 mmol/L, at least 14 mmol/L, at least 15 mmol/L, at least 16 mmol/L, or at least 17 mmol/L at the onset of treatment with the composition;   has a 2-hour postprandial plasma glucose excursion of at least 5 mmol/L, at least 5.5 mmol/L, at least 6 mmol/L, at least 6.5 mmol/L, or at least 7 mmol/L at the onset of treatment with the composition;   does not receive a GLP-1 receptor agonist or/and an insulin;   receives the composition parenterally;   is at least 50 years old;   has a body mass index of at least 30 kg/m 2 , at least 31 kg/m 2 , at least 32 kg/m 2  or at least 33 kg/m 2 ; or   has diabetes mellitus type 2 not adequately controlled with a treatment of at least 1.5 g/day of metformin.   
     
     
         25 . A method of treatment of diabetes mellitus type 1 or/and type 2, comprising administering to a subject in need thereof a composition comprising
 (a) lixisenatide or/and a pharmaceutically acceptable salt thereof, and   (b) insulin glargine or/and a pharmaceutically acceptable salt thereof,   wherein the compound (b) and compound (a) are present in a ratio of about 1.6 to about 2.4 U of compound (b) per μg of compound (a).   
     
     
         26 . The method of  claim 25 , wherein the compound (b) and compound (a) are present in the composition in a ratio of about 2 U of compound (b) per μg of compound (a). 
     
     
         27 . The method of  claim 25 , wherein the patient to be treated:
 is obese;   has diabetes mellitus type 2 not adequately controlled with metformin alone;   has a HbA1c value in the range of at least 7%, at least 8% or at least 9% at the onset of treatment with the composition;   has a fasting plasma glucose concentration of at least 7 mmol/L, at least 8 mmol/L, at least 9 mmol/L, at least 10 mmol/L, or at least 11 mmol/L at the onset of treatment with the composition;   has a self-monitored plasma glucose concentration of at least 8 mmol/L, at least 9 mmol/L, at least 10 mmol/L, or at least 11 mmol/L at the onset of treatment with the composition;   has a 2-hour postprandial plasma glucose of at least 12 mmol/L at least 13 mmol/L, at least 14 mmol/L, at least 15 mmol/L, at least 16 mmol/L, or at least 17 mmol/L at the onset of treatment with the composition;   has a 2-hour postprandial plasma glucose excursion of at least 5 mmol/L, at least 5.5 mmol/L, at least 6 mmol/L, at least 6.5 mmol/L, or at least 7 mmol/L at the onset of treatment with the composition;   does not receive a GLP-1 receptor agonist or/and an insulin;   receives the composition parenterally;   is at least 50 years old;   has a body mass index of at least 30 kg/m 2 , at least 31 kg/m 2 , at least 32 kg/m 2  or at least 33 kg/m 2 ; or   has diabetes mellitus type 2 not adequately controlled with a treatment of at least 1.5 g/day of metformin.