Safety, Pharmacokinetics, and Pharmacodynamics of Oral Insulin Administration in Healthy Subjects: A Randomized, Double‐Blind, Phase 1 Trial

Abstract Oral delivery is an ideal method of insulin administration and is currently a promising research field. Here, we evaluated the safety, pharmacokinetic, and pharmacodynamic characteristics of oral administration of an insulin capsule (ORMD‐0801) with 2 different sources of recombinant human insulin. This was a single‐center, randomized, double‐blind, placebo‐controlled, dose‐escalating phase 1 trial. Single dosing of the oral insulin capsule was administered in 70 healthy Chinese subjects. In stage 1, four dose groups (8, 16, 32, and 48 mg) for capsules containing Sanofi insulin and in stage 2, three dose groups (8, 32, and 48 mg) containing Hefei Tianmai insulin were evaluated consequently. The results showed that the oral insulin formulations with either source in the dose range 8 to 48 mg were safe, and no serious adverse events were observed. After a standard breakfast 45 minutes after dosing, the area under the concentration‐time curve (AUC) from time 0 to time t and AUC from time 0 to infinity for insulin in the 8‐mg and 48‐mg dose groups in stage 1 and for 8‐ to 48‐mg groups in stage 2 were slightly increased compared with placebo, but no significant dose‐related changes in the pharmacokinetic parameters were observed for either stage. The peak‐valley difference and the change in value of the AUC for glucose from baseline showed a dose‐related increase in the dose range from 8 to 48 mg in both stages. Together, this study indicated that in healthy Chinese subjects, this oral capsule containing 2 different insulin formulations was safe and well tolerated after a single‐dose administration.