Open AccessImpact of Insulin Tregopil and Its Permeation Enhancer on Pharmacokinetics of Metformin in Healthy Volunteers: Randomized, Open‐Label, Placebo‐Controlled, Crossover Study
Author(s) -
Khedkar Anand,
Lebovitz Harold,
Fleming Alexander,
Cherrington Alan,
Jose Vinu,
Athalye Sandeep N.,
Vishweswaramurthy Ashwini
Publication year - 2019
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12609
Subject(s) - metformin , pharmacokinetics , bioavailability , crossover study , bioequivalence , medicine , placebo , pharmacology , glycemic , insulin , confidence interval , type 2 diabetes , diabetes mellitus , endocrinology , alternative medicine , pathology
Oral insulin tregopil ( IN ‐105; a new drug under development) may be coadministered with oral antidiabetic drugs, such as metformin in patients with type 2 diabetes mellitus for optimal glycemic control. IN ‐105 has sodium caprate excipient, a permeation enhancer, for enhancing absorption in the stomach and increasing bioavailability via an oral route. Sodium caprate may increase bioavailability of metformin by a similar mechanism. Therefore, it was necessary to study the effect of IN ‐105 on pharmacokinetics (PKs) of metformin. In this randomized, open‐label, cross‐over study, metformin was administered to healthy volunteers receiving IN ‐105/placebo under fed/fasting conditions. The 90% confidence interval ( CI ) of the geometric mean ratio of the area under the curve from time zero to infinity ( AUC 0‐inf ; fasting and fed) and peak plasma concentration (C max ; fed) of metformin were within 0.80–1.25 acceptance range. Under fasting conditions, the upper bound margin of C max 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 PKs of metformin under fasting/fed conditions, and it was safe.