Pharmaceutical Composition Comprising a GLP-1-Agonist and Methionine
A liquid composition comprising a GLP-1 agonist or/and a pharmacologically tolerable salt thereof and, optionally, at least one pharmaceutically acceptable excipient, wherein the composition comprises methionine, as add-on therapy with metformin and/or with long-acting insulin/insulin derivates where appropriate.
1 . An aqueous liquid composition consisting essentially of:
(a) desPro 36 exendin-4(1-39)-Lys 6 -NH2 (“AVE0010”) or a pharmacologically tolerable salt thereof at a concentration of about 0.025 mg/mL to about 0.1 mg/mL;
(b) insulin glargine or a pharmacologically tolerable salt thereof at a concentration of about 3.64 mg/mL;
(c) L-methionine; and
(d) water.
2 . The aqueous liquid composition of claim 1 , wherein the composition exhibits chemical integrity after storage for 6 months at a temperature of +25° C.
3 . The aqueous liquid composition of claim 2 , wherein at least 80% of the liquid composition's active substance is in a substantially chemically unchanged form after storage for 6 months at a temperature of +25° C.
4 . The aqueous liquid composition of claim 2 , wherein the percentage of oxidized methionine with respect to the entire methionine content of the GLP-1 agonist after storage for 6 months at a temperature of +25° C. is below 0.7%.
5 . The aqueous liquid composition of claim 2 , wherein the proportion of total impurities with respect to the entire mass of the GLP-1 agonist present in the composition after storage for 6 months at +25° C. is below 10%.
6 . The aqueous liquid composition of claim 2 , wherein the proportion of proteins of high molecular weight with respect to the entire mass of the GLP-1 agonist in the composition after storage for 6 months at +25° C. is below 0.8%.
7 . An aqueous liquid pharmaceutical composition comprising the following constituents per 1 mL volume of the composition:
(a) approximately 50 μg desPro 36 exendin-4(1-39)-Lys 6 -NH 2 (“AVE0010”) or a pharmacologically tolerable salt thereof;
(b) approximately 3.5 mg sodium acetate trihydrate;
(c) approximately 2.7 mg m-cresol;
(d) approximately 3.0 mg L-methionine;
(e) approximately 18.0 mg glycerol; and
(f) water,
wherein the composition has improved stability and chemical integrity; and
wherein the composition has improved compatibility in intramuscular or subcutaneous administration.
8 . An aqueous liquid pharmaceutical composition comprising the following constituents per 1 mL volume of the composition:
(a) approximately 100 μg desPro 36 exendin-4(1-39)-Lys 6 -NH 2 (“AVE0010”) or a pharmacologically tolerable salt thereof;
(b) approximately 3.5 mg sodium acetate trihydrate;
(c) approximately 2.7 mg m-cresol;
(d) approximately 3.0 mg L-methionine;
(e) approximately 18.0 mg glycerol; and
(f) water,
wherein the composition has improved stability and chemical integrity; and
wherein the composition has improved compatibility in intramuscular or subcutaneous administration.