Impact of Insulin Tregopil and its Permeation Enhancer on Pharmacokinetics of Metformin in Healthy Volunteers: Randomized, Open-label, Placebo Controlled, Crossover Study.

Oral insulin tregopil (IN-105; new drug under development) may be co-administered with oral anti-diabetic drugs such as metformin in type 2 diabetes mellitus patients for optimal glycemic control. IN-105 has sodium caprate excipient, a permeation enhancer, for enhancing absorption in stomach and increasing bioavailability via oral route. Sodium caprate may increase bioavailability of metformin by a similar mechanism. Therefore, it was necessary to study effect of IN-105 on pharmacokinetics of metformin. In this randomized, open-label, cross-over study, metformin was administered to healthy volunteers receiving IN-105/placebo under fed/fasting conditions. 90% CI of GMR of AUC0-inf (fasting and fed) and Cmax (fed) of metformin were within 0.80-1.25. Under fasting conditions, upper bound margin of Cmax was just beyond this range (i.e. 1.27) and was concluded as functionally not relevant. There was no clinically significant effect of sodium caprate/IN-105 on pharmacokinetics of metformin under fasting/fed conditions and it was safe. This article is protected by copyright. All rights reserved.