OR14-1 Pharmacodynamics, Safety, Tolerability, and Efficacy of Oral Insulin Formulation (Oshadi Icp) among Young Adults with Type 1 Diabetes: A Summary of Clinical Studies Phases I, Ib, and Ii

Abstract

Background Replacement of subcutaneous (SC) insulin by oral insulin for Type I diabetes (T1D) could promote patient compliance and minimize hyperinsulinemia. Oshadi Drug Administration Ltd. has developed an oral carrier for proteins delivery, composed of known ingredients, including polysaccharides and nano-silica , and based on quantum theory of biochemical reactions. Objectives To assess the pharmacodynamics of Oshadi oral insulin formulation (Oshadi-I) and the safety, tolerability and glucose-lowering effect of Oshadi oral insulin, proinsulin and c-peptide formulation (Oshadi-Icp) in young patients with T1D. Methods Phase I: a single blinded crossover between Oshadi-I and placebo. Glucose concentration was followed over 13 hours post a single dose. Phase Ib: a crossover open label comparison between 2 sessions of 3 days of Oshadi-Icp or placebo. During both sessions patients stayed at the research unit, provided with identical low carbs diet and minimal doses of SC insulin. Phase II:a prospective 4 weeks open-label follow-up of patients using an insulin pump combined with Oshadi-Icp at home. During Phases Ib and II iinterstitial glucose (IG) was monitored by CGMS, and capillary glucose by finger pricks (CG). Mean IG, mean CG, their area under the curve (AUC), weight adjusted total daily dose (TDD) of SC insulin, BMI, HbA1c, fructosamine, and safety parameters were compared. Results Eight patients, mean age 27.7±4.8 years, 5 males, were included in Phase I study, 10 patients mean age 26.2±4.7 years, 7 males, were included in Phase Ib study, and 16 patients mean age 23.5± 4.6 years, 12 males, were included in Phase II study. Oshadi-Icp was well tolerated, with no adverse events nor clinically relevant changes in vital signs, electrocardiograms, and standard safety laboratory parameters during all study phases. Phase I demonstrated a significantly lower plasma glucose AUC within 7 hours post Oshadi-I compared with placebo: 1116.1mg/dl±107.0 vs. 1345.7mg/dl ±82.0, p <0.01. Phase Ib study demonstrated significantly lower mean post meals GC, AUC-GC and mean insulin TDD at the third day during Oshadi-Icp session compared to placebo: 207.5mg/dl± 6.0 vs. 265.4mg/dl±3.9, p<0.001, 3107.57mg/dl±20.5 vs. 4031.58mg/dl±26.76, p<0.001, 0.14 ±0.04 IU/kg/day vs. 0.18 ±0.06 IU/kg/day, p≤0.01. Four episodes of GC ≤70mg/dL were detected during the Oshadi Icp session and 1 episode of mild DKA was detected during the placebo session. Phase II study demonstrated the ratio of SC insulin dose to carbohydrate intake was significantly lower during Oshasi-Icp month 78-80% for each week compared to baseline 100%. Fructosamine was stable throughout the study, with no episodes of severe hypoglycemia and DKA. Conclusions A substantial safety and glucose lowering effect of Oshadi-Icp formulation were demonstrated. Its clinical potential and beneficial effect for patients with T1D should be further studied.