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 pharmaceutical composition comprising:
(a) 0.01 mg/mL to 1.5 mg/mL desPro 36 exendin-4(1-39)-Lys 6 -NH 2 (“AVE0010”) and/or a pharmacologically tolerable salt thereof;
(b) methionine; and
(c) water,
wherein the composition is substantially free of histidine.
2. The aqueous liquid composition of claim 1 , wherein the composition further comprises a pharmaceutically acceptable preservative.
3. The aqueous liquid composition of claim 2 , wherein the pharmaceutically acceptable preservative is m-cresol.
4. The aqueous liquid composition of claim 1 , wherein the composition further comprises glycerol.
5. The aqueous liquid composition of claim 1 , wherein the pH of the composition ranges from 3.5 to 5.
6. The aqueous liquid composition of claim 1 , wherein the concentration of methionine ranges from 0.5 mg/mL to 20 mg/mL.
7. The aqueous liquid composition of claim 6 , wherein the concentration of methionine ranges from 1 mg/mL to 5 mg/mL.
8. The aqueous liquid composition of claim 1 , wherein the composition exhibits chemical integrity after storage for 6 months at a temperature of +25° C.
9. The aqueous liquid composition of claim 8 , 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.
10. The aqueous liquid composition of claim 8 , 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%.
11. The aqueous liquid composition of claim 8 , 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%.
12. The aqueous liquid composition of claim 8 , 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%.
13. The aqueous liquid composition of claim 1 , comprising:
(a) 0.01 mg/mL to 1.5 mg/mL AVE0010 and/or a pharmacologically tolerable salt thereof;
(b) sodium acetate;
(c) m-cresol;
(d) L-methionine;
(e) glycerol; and
water,
wherein the composition is substantially free of histidine.
14. The aqueous liquid composition of claim 13 , wherein the composition is substantially free of ethylenediaminetetraacetic acid (EDTA).
15. The aqueous liquid composition of claim 13 , wherein the concentration of AVE0010 is about 0.01 mg/mL to about 0.5 mg/mL.
16. The aqueous liquid composition of claim 13 , wherein the composition has a pH of about 4.5.
17. The aqueous liquid composition of claim 1 , wherein the composition is an injectable composition.
18. The aqueous liquid composition of claim 1 , wherein the composition further comprises at least one pharmaceutically acceptable excipient.
19. The aqueous liquid composition of claim 1 , wherein the composition is suitable for parenteral administration.
20. The aqueous liquid composition of claim 1 , wherein the composition is substantially free of ethylenediaminetetraacetic acid (EDTA).
21. The aqueous liquid composition of claim 1 , wherein the composition comprises at least 50% w/w of water.
22. The aqueous liquid composition of claim 1 , further comprising a buffer.
23. The aqueous liquid composition of claim 22 , wherein the buffer is acetate, phosphate, or citrate.
24. The aqueous liquid composition of claim 22 , wherein the buffer is acetate.
25. The aqueous liquid composition of claim 1 , wherein the concentration of AVE0010 is about 50 μg/mL to about 100 μg/mL.
26. The aqueous liquid composition of claim 1 , wherein the concentration of AVE0010 is about 33 μg/mL to about 50 μg/mL.
27. The aqueous liquid composition of claim 1 , wherein the concentration of AVE0010 is about 0.01 mg/mL to about 0.5 mg/mL.
28. The aqueous liquid composition of claim 1 , wherein the concentration of AVE0010 is about 33 μg/mL.
29. The aqueous liquid composition of claim 1 , wherein the concentration of AVE0010 is about 50 μg/mL.
30. The aqueous liquid composition of claim 1 , wherein the concentration of AVE0010 is about 100 μg/mL.