Dose response to oral insulin capsules in fasting, healthy subjects

Oral alternatives to injectable insulins are expected to better mimic physiological portal vein insulin gradients, while inducing far fewer side effects than systemically delivered insulins. After establishing safety and efficacy of an insulin capsule (ORMD-0801), the presented research efforts set out to explore the ideal dose and active ingredient:adjuvant ratios by evaluating dose-responses of healthy, fasting individuals treated with orally administered insulin (ORMD-0801). One capsule containing 8 mg insulin, two capsules of 8 mg insulin each (8+8mg) or one capsule of 16 mg insulin were administered to subjects, followed by a 300-min monitoring period. Interim analyses demonstrated responses in 7/10 subjects, with maximal blood glucose responses for all treatments observed following a lag of ≥60 min from administration, as expected of an enteric-coated capsule. Dose response was manifested by significantly lower mean blood glucose Cmin following the 8+8mg (47.9 ± 11.3 mg/dL, p=0.006) and 16mg (57.3 ± 8.4 mg/dL, p=0.001) treatments, when compared to that which followed 8mg dosing (64.6 ± 6.2 mg/dL). Significant reductions in glucose area under the curve (AUC) values were observed following both 8+8mg and 16mg treatments (13.2% and 8.1%, respectively), when compared to 8mg (p=0.003 and 0.008, respectively). No adverse events were reported or observed following any of the treatments. In conclusion, increasing doses of ORMD-0801 were well tolerated by healthy individuals and response intensity positively correlated with the administered dose.