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

Background Oral 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. Methods After an overnight fast, 44 healthy males received single fixed doses of oral insulin 338 administered 0, 30, 60 or 360 min before consuming a standardised meal (500 kcal, 57 energy percent [E%] carbohydrate, 13 E% fat, 30 E% protein). Blood samples for pharmacokinetic assessment were taken up to 288 h post-dose. Results Total exposure (area under the concentration-time curve from time zero to infinity [AUC Ins338,0–∞ ]) and maximum concentration ( C max,Ins338 ) of insulin 338 were both significantly lower for 0 versus 360 min post-dose fasting (ratio [95% confidence interval (CI)]: 0.36 [0.26–0.49], p < 0.001, and 0.35 [0.25–0.49], p < 0.001, respectively). There were no significant differences in AUC Ins338,0–∞ and C max,Ins338 for 30 or 60 versus 360 min post-dose fasting (ratio [95% CI] 30 versus 360 min: 0.85 [0.61–1.21], p = 0.36, and 0.86 [0.59–1.26], p = 0.42; ratio [95% CI] 60 versus 360 min: 0.96 [0.72–1.28], p = 0.77, and 0.99 [0.75–1.31], p = 0.95). The mean half-life was ~ 55 h independent of the post-dose fasting period. Oral insulin 338 was well-tolerated with no safety issues identified during the trial. Conclusions Oral insulin 338 pharmacokinetics are not affected by food intake from 30 min after dosing, implying that patients with diabetes mellitus do not need to wait more than 30 min after a morning dose of oral insulin 338 before having their breakfast. This is considered important for convenience and treatment compliance. ClinicalTrials.gov identifier NCT02304627.