BUFFERED FORMULATIONS OF EXENDIN (9-39)
Provided herein are liquid pharmaceutical formulations comprising exendin (9-39) or a pharmaceutically acceptable salt thereof and a tonicity modifier in a physiologically acceptable buffer having a pH in the range of about 5 to about 6. In some embodiments, the buffered liquid formulation comprises exendin (9-39) or a pharmaceutically acceptable salt thereof in an acetate buffer or a citrate buffer. Methods of treating or preventing hyperinsulinemic hypoglycemia in a subject comprising administering to the subject the buffered liquid formulation are also provided.
1 . A liquid pharmaceutical formulation comprising exendin (9-39) or a pharmaceutically acceptable salt thereof and a tonicity modifier in a physiologically acceptable buffer,
wherein the tonicity modifier comprises mannitol,
wherein the physiologically acceptable buffer comprises an acetate buffer, and
wherein liquid pharmaceutical formulation has a pH of about 5.5.
2 . The liquid pharmaceutical formulation of claim 1 , wherein the pharmaceutically acceptable salt of exendin (9-39) is exendin (9-39) acetate.
3 . The liquid pharmaceutical formulation of claim 1 , wherein the physiologically acceptable buffer comprises sodium acetate.
4 . The liquid pharmaceutical formulation of claim 3 , wherein the physiologically acceptable buffer comprises sodium acetate at a concentration of about 10 mM.
5 . The liquid pharmaceutical formulation of claim 1 , wherein the exendin (9-39) or the pharmaceutically acceptable salt thereof is at a concentration of about 10 mg/mL to about 120 mg/mL.
6 . The liquid pharmaceutical formulation of claim 5 , wherein the exendin (9-39) or the pharmaceutically acceptable salt thereof is at a concentration of about 100 mg/mL.
7 . The liquid pharmaceutical formulation of claim 1 , wherein the mannitol is present in an amount from about 20 mg/mL to about 60 mg/mL.
8 . The liquid pharmaceutical formulation of claim 1 , wherein the mannitol is present in an amount that achieves an osmolality of about 275 to 300 mOsm/kg.
9 . The liquid pharmaceutical formulation of claim 1 , wherein the mannitol is present in an amount that achieves an osmolality of about 290 mOsm/kg.
10 . The liquid pharmaceutical formulation of claim 1 , formulated for subcutaneous administration.
11 . The liquid pharmaceutical formulation of claim 1 , wherein the exendin (9-39) or the pharmaceutically acceptable salt thereof does not exhibit detectable aggregation in the formulation.
12 . The liquid pharmaceutical formulation of claim 1 , wherein the exendin (9-39) or the pharmaceutically acceptable salt thereof does not precipitate out of the formulation.
13 . The liquid pharmaceutical formulation of claim 12 , wherein the exendin (9-39) or the pharmaceutically acceptable salt thereof does not precipitate out of the formulation at 5° C.
14 . A method of treating or preventing hyperinsulinemic hypoglycemia in a subject, the method comprising administering to the subject the liquid pharmaceutical formulation of claim 1 .
15 . The method of claim 14 , wherein the subject previously had an upper-gastrointestinal procedure.
16 . The method of claim 14 , wherein the subject previously had a bariatric procedure.
17 . The method of claim 14 , wherein the subject has post-bariatric hypoglycemia (PBH).
18 . The method of claim 14 , wherein the method comprises subcutaneously administering to the subject the liquid pharmaceutical formulation once per day (QD) or twice per day (BID).
19 . The method of claim 14 , wherein the method comprises subcutaneously administering to the subject the liquid pharmaceutical formulation at a total daily dosage of about 90 mg.
20 . The method of claim 14 , wherein the method comprises subcutaneously administering to the subject the liquid pharmaceutical formulation at a dosage of about 90 mg QD.