The Effect of Food Intake on the Pharmacokinetics of Oral Basal Insulin: A Randomised Crossover Trial in Healthy Male Subjects

Abstract

BackgroundOral insulin 338 is a novel tablet formulation of a long-acting basal insulin. This randomised, open-label, four-period crossover trial investigated the effect of timing of food intake on the single-dose pharmacokinetic properties of oral insulin 338.MethodsAfter an overnight fast, 44 healthy males received single fixed doses of oral insulin 338 administered 0, 30, 60 or 360\xa0min before consuming a standardised meal (500\xa0kcal, 57\xa0energy percent [E%] carbohydrate, 13\xa0E% fat, 30\xa0E% protein). Blood samples for pharmacokinetic assessment were taken up to 288\xa0h post-dose.ResultsTotal exposure (area under the concentration-time curve from time zero to infinity [AUCIns338,0–∞]) and maximum concentration (Cmax,Ins338) of insulin 338 were both significantly lower for 0 versus 360\xa0min post-dose fasting (ratio [95% confidence interval (CI)]: 0.36 [0.26–0.49], p\u2009<\u20090.001, and 0.35 [0.25–0.49], p\u2009<\u20090.001, respectively). There were no significant differences in AUCIns338,0–∞ and Cmax,Ins338 for 30 or 60 versus 360\xa0min post-dose fasting (ratio [95% CI] 30 versus 360\xa0min: 0.85 [0.61–1.21], p\u2009=\u20090.36, and 0.86 [0.59–1.26], p\u2009=\u20090.42; ratio [95% CI] 60 versus 360\xa0min: 0.96 [0.72–1.28], p\u2009=\u20090.77, and 0.99 [0.75–1.31], p\u2009=\u20090.95). The mean half-life was\u2009~\u200955\xa0h independent of the post-dose fasting period. Oral insulin 338 was well-tolerated with no safety issues identified during the trial.ConclusionsOral insulin 338 pharmacokinetics are not affected by food intake from 30\xa0min after dosing, implying that patients with diabetes mellitus do not need to wait more than 30\xa0min after a morning dose of oral insulin 338 before having their breakfast. This is considered important for convenience and treatment compliance.ClinicalTrials.gov identifierNCT02304627.