An open‐label, multiple ascending dose trial of orally administered insulin Tregopil in patients with type 1 diabetes mellitus to evaluate its pharmacokinetics, pharmacodynamics, safety and tolerability

Abstract Aim This trial evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of oral insulin Tregopil (Part 1; results discussed in this paper) and the post‐prandial glucose control with different meal types in comparison with insulin aspart (Part 2) in patients with type 1 diabetes mellitus (T1DM). Materials and Methods This Phase 1, open‐label, multiple ascending dose (30/45/60 mg/60 + 30 mg rescue insulin Tregopil) trial enrolled 37 patients with T1DM (3 female [8.1%], 34 male [91.9%]; median age: 39.5 years). Following screening, patients entered a run‐in phase to optimize their basal‐bolus (insulin glargine and insulin aspart) insulin therapy, and insulin Tregopil was administered orally 10 min before the three major meals of the day in all cohorts during this period. Safety assessments included adverse events and hypo−/hyperglycaemic episodes, vital signs, electrocardiograms, laboratory safety parameters and physical examination. PK and PD were the secondary objectives. Results The overall safety profile of insulin Tregopil indicated no safety concerns except a PD effect (hypoglycaemia). The incidence of hypoglycaemia did not increase with increasing doses of insulin Tregopil, and none of the episodes were severe. In general, the variability of the PK/PD parameters was high. Insulin Tregopil demonstrated a rapid onset of action, with peak blood concentrations reached within 15–20 min post‐dosing. Subsequently, insulin Tregopil exerted a PD effect for up to 105 min. Conclusion Fixed‐dose insulin Tregopil reduced the requirement for insulin aspart supplementation, although it was not a viable stand‐alone option for the daily management of T1DM. Insulin Tregopil could be explored with a flexible dosing approach and be titrated based on individual needs. Trial Registration The trial is registered at Clinicaltrials.gov (CT.gov identifier: NCT04141423). The ethical approval number for the protocol is 2019146.