A Novel Per-Oral Insulin Formulation for Human Subjects
Abstract Number: 526-P
Abstract Category: Clinical Therapeutics/New Technology
Abstract Scheduled: Exhibit Hall
Saturday - June 15 2002
Authors: MIRIAM KIDRON
YORAM MENACHEM
BRUCE VARIANO
EHUD ARBIT
STEVE DINH
MICHAEL GOLDBERG
HANOCH BAR-ON.
Diabetes mellitus in its two types, especially type 1, is treated with insulin. Insulin is a peptide, therefore it is administered by the parenteral route, usually subcutaneously. Much effort and research have been invested in finding alternative routes of insulin administration, namely, nasal, dermal, pulmonary, and oral. In this report we present data indicating that the combination of insulin and an EMISPHERE delivery agent enables the absorption of insulin from the gastrointestinal tract.[br]Capsules containing the combination of the delivery agent and increasing doses of insulin were administered orally, as a single dose, to 12 non-diabetic volunteers in order to assess tolerability and biological response. Plasma glucose, insulin and C-peptide concentrations were determined. In all cases a hypoglycemic effect was demonstrated following an increase in plasma insulin levels. The nadir of plasma glucose appeared 30-50 minutes following the oral dose, suggesting that the absorption site is in the upper part of the gastro-intestinal tract, likely the duodenum. Also, plasma C-peptide levels were suppressed in accord with increasing amount of exogenous insulin absorbed, pointing to the fact that the secretion of endogenous hormone is partially abolished. We observed a 50% reduction of blood glucose levels, as well as in C-peptide levels, with the higher oral insulin doses. No adverse effects were detected during the study or up to 12 weeks after dosing. In conclusion, using an Emisphere oral delivery agent, the oral dosing of insulin appears practical.
Oral Insulin: Pharmacokinetics and Pharmacodynamics of Human Insulin Following Oral Administration of an Insulin/Delivery Agent Capsule in Healthy Volunteers
Abstract Number: 197-OR
Abstract Category: Clinical Therapeutics
Abstract Scheduled: GW104-C
Sunday - June 16 2002
Authors: RICHAT ABBAS
ANDREA LEONE-BAY
RAJESH K. AGAWAL
SHINGAI MAJURU
PAUL ROLAN
CYRIL CLARKE
COLIN SCOTT
EHUD ARBIT
ROBERT A. BAUGHMAN.
Objectives: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of human insulin following oral administration in healthy subjects. Oral insulin absorption was facilitated by an EMISPHERE[reg] oral delivery agent (DA). Methods: Three groups of fasted, healthy volunteers participated in this double-blind, placebo-controlled study. In group one, 9 subjects received 4 escalating oral doses of DA capsules or placebo. In group two, 10 subjects received one single subcutaneous dose of insulin, and two escalating single oral doses of insulin/DA capsules or placebo. In group three, 10 subjects received another 3 escalating oral doses of insulin/DA capsules or placebo followed by a single oral dose of insulin alone (150 units). Blood samples were collected serially up to 6 hours, and analyzed for glucose, insulin, and C-peptide. Results: Following oral administration of the insulin/DA capsules, insulin was rapidly absorbed into the systemic circulation and plasma concentrations peaked (Cmax) within 25 min. The corresponding maximum reductions in both plasma glucose and C-peptide concentrations occurred within 1 hour. Table 1: Insulin alone or DA alone dosed orally did not affect plasma insulin or glucose levels. No serious adverse events were reported. The most common adverse event was hypoglycemia. All doses were well tolerated. This study demonstrates that oral administration of capsules containing the insulin/DA combination provides insulin absorption at clinically significant levels. |
