Biocon Limited has announced the results of an ascending dose study with oral insulin drug (IN-105) at the European Association for the Study of Diabetes (EASD) meeting in Rome. The study involved dosing type-2 diabetes subjects with single doses of 0 mg (placebo), 10 mg, 15 mg, 20 mg and 30 mg tablets of IN-105 in 5 separate periods before a mixed 600 kcal breakfast. The outcome measurements were the safety and tolerability of IN-105, as well as the pharmacokinetics and pharmaco-dynamics of IN-105. The results showed that IN-105 was safe and well tolerated by patients.
Absorption of IN-105 was proportional to the dose administered; a serum average Cmax of 350 milliunits /litre was reached at 30 minutes post dosing at the highest dose of 30 mg. The resulting glucose drops showed linearity with respect to the dose. The two-hour postprandial glucose rise over baseline for the 10, 15, 20 and 30 mg doses were 15.3, 24.1, 31.3 and 49.5 mg/dL lower than the corresponding rise for placebo. There were no symptomatic hypoglycaemic events observed at any of the doses. Due to the rapid pharmacokinetics of the drug, there were transient values of hypoglycaemia seen soon after the administration of the drug; however these values did not result in any symptoms due to the rapid alleviation of glucose levels due to the meal that followed the drug.
C-peptide values were also significantly depressed over all the doses tested, indicating a possibility of beta cell rest in patients dosed with IN-105. Longer term, six-month, studies are being planned in type-2 diabetic subjects to understand the impact of chronic dosing of IN-105 on postprandial glucose control and glycated haemoglobin.
"The present study shows that IN105 delivers physiologically active insulin orally in concentrations sufficient to decrease post-meal hyperglycemias and to decrease the burden of the meal on endogenous insulin secretion. These data support the feasibility of providing insulin orally to treat postprandial hyperglycaemia in diabetic patients" affirmed Dr Harold E Lebovitz, Professor of Medicine, Endocrinology and Diabetes State University of New York Health Science Center at Brooklyn.
"The data presented here show that insulin can be reliably delivered in individuals with type-2 diabetes via the oral route. Further the administered insulin improved control post meal plasma glucose without causing symptomatic hypoglycaemia. Such data support the feasibility of oral insulin delivery as a therapeutic option," said Prof Alan D Cherrington, Professor of Molecular Physiology & Biophysics, Professor of Medicine, Vanderbilt University.
IN-105 is a novel analog of insulin, proprietary to Biocon. The product has special properties that make it feasible for delivery in tablet form stable at room temperature. The advantages of tablet delivery go beyond the obvious. Besides being a needle-free insulin, this method of delivery allows IN-105 to be delivered into the body in a physiological manner that mimics the way that the pancreas release insulin into the circulation (i.e. into the portal vein). This contrasts with all the other known methods of delivery, including inhaled insulin, which brings in insulin from the periphery into the circulation.