TREATMENT OF TYPE 2 DIABETES OR OBESITY OR OVERWEIGHT WITH 2-[(4-{6-[(4-CYANO-2-FLUOROBENZYL)OXY]PYRIDIN-2-YL}PIPERIDIN-1-YL)METHYL]-1-[(2S)-OXETAN-2-YLMETHYL]-1H-BENZIMIDAZOLE-6-CARBOXYLIC ACID OR A PHARMACEUTICALLY SALT THEREOF
The invention provides a method for treating T2DM, obesity or overweight or for weight management control by administering to an mammal (e.g. a human) in need thereof a pharmaceutical composition twice daily in an oral dosage form, wherein the pharmaceutical composition contains 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-5 [(2S)-oxetan-2-ylmethyl]-1H-benzimidazole carboxylic acid, or a pharmaceutically salt thereof [such as its tris salt]. Moreover, the invention provides oral compositions/formulations for the methods of treatment described herein.
1 . A method for treating T2DM comprising administering to a human in need thereof a pharmaceutical composition, wherein:
the pharmaceutical composition is in an oral dosage form; and
the pharmaceutical composition comprises 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid or a pharmaceutically salt thereof.
2 . The method of claim 1 , wherein the pharmaceutical composition is in an immediate-release solid dosage form.
3 . The method of claim 1 , wherein the pharmaceutical composition is in an immediate-release tablet dosage form.
4 . The method of claim 1 , wherein the pharmaceutical composition comprises 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid or a pharmaceutically salt thereof in an amount equivalent to about 10 mg to about 140 mg of 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid.
5 . The method of claim 4 , wherein the 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid or pharmaceutically salt thereof in the pharmaceutical composition is tris salt of 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid.
6 . The method of claim 4 , wherein the pharmaceutical composition is administered twice daily.
7 . The method of claim 6 , wherein the two daily administrations are separated by at least about 8 hours.
8 . The method of claim 6 , wherein the treating D2TM comprises improving glycemic control.
9 . A method for weight management control or for treating obesity or overweight comprising administering to a human in need thereof a pharmaceutical composition, wherein:
the pharmaceutical composition is in a solid oral dosage form; and
the pharmaceutical composition comprises 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid or a pharmaceutically salt thereof.
10 . The method of claim 9 , wherein the pharmaceutical composition comprises 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid or a pharmaceutically salt thereof in an amount equivalent to about 10 mg to about 140 mg of 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid.
11 . The method of claim 10 , wherein the pharmaceutical composition is administered twice daily.
12 . The method of claim 11 , wherein the two daily administrations are separated by at least about 8 hours.
13 . (canceled)
14 . An immediate-release oral pharmaceutical composition comprising:
2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid, or a pharmaceutically acceptable salt thereof;
a filler;
a disintegrant; and
a lubricant.
15 . The pharmaceutical composition of claim 14 wherein:
the 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid or a pharmaceutically acceptable salt thereof is tris salt of 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid;
the filler comprises microcrystalline cellulose, lactose, or a combination thereof;
the disintegrant is sodium starch glycolate; and
the lubricant is magnesium stearate or sodium stearyl fumarate.
16 . The pharmaceutical composition of claim 14 wherein:
the 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid or a pharmaceutically acceptable salt thereof is tris salt of 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid;
the filler comprises microcrystalline cellulose, lactose, or a combination thereof;
the disintegrant is crospovidone; and
the lubricant is magnesium stearate or sodium stearyl fumarate.
17 . The pharmaceutical composition of claim 14 , wherein:
the 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid or a pharmaceutically acceptable salt thereof comprises about 1.0% to about 35.0% by weight;
the filler comprises about 60% to about 95% by weight;
the disintegrant comprises about 1.0% to about 5.0% by weight; and
lubricant comprises about 0.2% to about 2.5% by weight.
18 . The pharmaceutical composition of claim 14 , wherein the composition comprise tris salt of 2-[(4-{6-[(4-cyano fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid in an amount equivalent to about 10 mg to about 120 mg of 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan ylmethyl]-1H-benzimidazole-6-carboxylic acid.
19 - 20 . (canceled)