AIM: The objective of the study was to establish the dose response of IN-105 tablets and explore a possible therapeutic window in type 2 diabetes subjects poorly controlled on metformin. METHODS: The primary objective was to examine the effect of sequential single ascending doses of IN-105 on the plasma glucose concentration under fed conditions. All subjects received, sequentially, matching placebo, 10, 15, 20 and 30 mg IN-105 tablets in five consecutive periods. Tablets were administered 20 min prior to meal in all the periods. Plasma levels of immunoreactive insulin, C-peptide and glucose were measured up to 180 min from the time of dosing. The changes in postprandial glucose levels at 120 min in response to IN-105 administration were also compared against those of placebo. RESULTS: Changes in glucose from baseline (mean +/- s.d.) at 140 min (2 h postprandial) were 94.84 +/- 22.3, 79.45 +/- 43.00, 70.68 +/- 35.71, 63.47 +/- 42.75 and 53.06 +/- 47.27 mg/dL, respectively, and exhibited linear dose-response. The insulin C(max) values were found to be 50.8 +/- 26.0 mU/L for placebo, 100.3 +/- 66.7 with 10 mg IN-105, 177.69 +/- 150.3 with 15 mg IN-105, 246.2 +/- 245.2 with 20 mg IN-105 and 352.5 +/- 279.3 mU/L with 30 mg of IN-105. CONCLUSIONS:IN-105 absorption is proportional to the dose administered. The 2-h postprandial glucose excursion was reduced in a dose proportional manner. Circulating C-peptide levels were found to be suppressed in proportion to the IN-105 exposure. IN-105 reduces glucose excursion despite lower endogenous insulin secretion. IN-105 seems to have a wide therapeutic window as no clinical hypoglycaemia was observed at any of the doses studied.
RCT Entities:
AIM: The objective of the study was to establish the dose response of IN-105 tablets and explore a possible therapeutic window in type 2 diabetes subjects poorly controlled on metformin. METHODS: The primary objective was to examine the effect of sequential single ascending doses of IN-105 on the plasma glucose concentration under fed conditions. All subjects received, sequentially, matching placebo, 10, 15, 20 and 30 mg IN-105 tablets in five consecutive periods. Tablets were administered 20 min prior to meal in all the periods. Plasma levels of immunoreactive insulin, C-peptide and glucose were measured up to 180 min from the time of dosing. The changes in postprandial glucose levels at 120 min in response to IN-105 administration were also compared against those of placebo. RESULTS: Changes in glucose from baseline (mean +/- s.d.) at 140 min (2 h postprandial) were 94.84 +/- 22.3, 79.45 +/- 43.00, 70.68 +/- 35.71, 63.47 +/- 42.75 and 53.06 +/- 47.27 mg/dL, respectively, and exhibited linear dose-response. The insulin C(max) values were found to be 50.8 +/- 26.0 mU/L for placebo, 100.3 +/- 66.7 with 10 mg IN-105, 177.69 +/- 150.3 with 15 mg IN-105, 246.2 +/- 245.2 with 20 mg IN-105 and 352.5 +/- 279.3 mU/L with 30 mg of IN-105. CONCLUSIONS: IN-105 absorption is proportional to the dose administered. The 2-h postprandial glucose excursion was reduced in a dose proportional manner. Circulating C-peptide levels were found to be suppressed in proportion to the IN-105 exposure. IN-105 reduces glucose excursion despite lower endogenous insulin secretion. IN-105 seems to have a wide therapeutic window as no clinical hypoglycaemia was observed at any of the doses studied.
Authors: V Akbari; F Hendijani; A Feizi; J Varshosaz; Z Fakhari; S Morshedi; S A Mostafavi Journal: J Endocrinol Invest Date: 2015-06-24 Impact factor: 4.256
Authors: Justin M Gregory; Margaret Lautz; Lindsey M Moore; Phillip E Williams; Praveen Reddy; Alan D Cherrington Journal: Diabetes Obes Metab Date: 2018-09-16 Impact factor: 6.577
Authors: Juan José Marín-Peñalver; Iciar Martín-Timón; Cristina Sevillano-Collantes; Francisco Javier Del Cañizo-Gómez Journal: World J Diabetes Date: 2016-09-15
Authors: Fa Liu; Jung-Eun Park; Wen-Jian Qian; Dan Lim; Martin Gräber; Thorsten Berg; Michael B Yaffe; Kyung S Lee; Terrence R Burke Journal: Nat Chem Biol Date: 2011-07-17 Impact factor: 15.040