Emisphere Technologies, Inc., a biopharmaceutical company, announced that results from a clinical study evaluating an oral insulin tablet prototype (the Emisphere oral insulin tablet) were presented in a plenary session at the Diabetes Technology Society's 3rd Annual Meeting, held on November 6 - November 8, 2003 in San Francisco, California.
The Phase I study was designed to test the performance of novel insulin tablet prototypes prepared with an Emisphere delivery agent when orally administered to type 2 diabetic patients who were subsequently either fasted or fed a standard meal. In addition to safety and tolerability, blood glucose, insulin and C-Peptide levels were monitored. The study demonstrated that an oral insulin prototype could be dosed very close to mealtime.
A single-blind crossover study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of insulin prepared in an oral tablet form with an Emisphere delivery agent (DA) in fasted and pre-prandial type 2 diabetic patients. Two dose ratios of insulin to DA were evaluated against control tablets (consisting of delivery agent only) in 8 male, diet-controlled, type 2 diabetic patients with fasting blood glucose and HbA1c lower than 150mg/dL and 8 per cent, respectively. The study was conducted at the Profil Institute in Germany.
The study consisted of six treatment periods. During five of these study periods, a single dose of oral insulin tablets at a specified insulin-to-DA ratio was administered after an overnight fast. During Periods 1 and 2, subjects were administered four 150 mg tablets, containing a total of 300 U Insulin/400 mg DA in the fasted and pre-prandial state (10 minutes before a standard, ADA breakfast), respectively. During Periods 3 and 4, subjects were administered two 125 mg tablets containing a total of 300 U Insulin/160 mg DA in the fasted and pre-prandial state (10 minutes before a standard, ADA breakfast), respectively. For Period 5, subjects were administered 300 U Insulin/ 160 mg DA in the pre-prandial state immediately before a standard, ADA breakfast. During Period 6, two control tablets containing a total of 200mg of DA were administered 10 minutes before a standard, ADA breakfast.
Blood samples were drawn at multiple time points and analyzed for insulin, C- peptide, and glucose levels.
In summary, the study results demonstrated that the Emisphere oral insulin tablets exhibited a rapid onset of action and produced a statistically significant reduction in post-prandial glucose excursion (a key therapeutic measurement for type 2 diabetes) when administered to type 2 diabetic patients 10 minutes before a mixed meal.
Tablets at both ratios of insulin and DA produced a significant decrease, based on preliminary data analysis, in post-prandial glucose excursion (p <0.0005) relative to the DA alone. This confirms that oral insulin can be dosed 10 minutes prior to a meal and still control post-prandial glucose excursion.
Neither serious adverse events (including those related to hypoglycemia) nor adverse events attributed by the clinician to the study drug were observed in this study. Thus, these oral insulin tablets appeared to be tolerated well by the type 2 diabetic patients in this study.
Further studies will continue to explore the dose ratio and food effect of oral insulin tablets. In addition, a multiple dose study in Type 2 diabetic patients has been initiated.
Ehud Arbit, M.D., vice president, Medical Research, stated during the Diabetes Technology Meeting, "These results are exciting and they represent an important milestone in the development of our oral insulin program. We have demonstrated that a practical tablet dosage form of insulin, which can be dosed just before mealtime and still reduce post-prandial glucose excursion, is feasible."
The ADA estimates that of the 17 million Americans with diabetes, 90-95 per cent are type 2 diabetics. The ADA recommends that patients with type 2 diabetes who are taking insulin should time their insulin dose so that it begins working as glucose from a meal enters the bloodstream (30-45 minutes before mealtime for regular insulin injections). Currently, all approved insulin therapies are in injectable form.
Emisphere's oral delivery of insulin has the potential to mimic the natural physiology of insulin release by targeting the liver first before being distributed to the peripheral circulation, so that the rate and location of naturally secreted insulin release are replicated. Orally delivered insulin with the appropriate clinical attributes may provide a more convenient and effective diabetes therapy with fewer complications compared to existing medical treatments, and may be useful in halting the progression of early stage diabetes.
Emisphere's broad-based oral drug delivery technology platform, known as the eligen technology, is based on the use of proprietary, synthetic chemical compounds, known as Emisphere delivery agents, or "carriers". These molecules enable the transport of the therapeutic macromolecules across biological membranes such as the small intestine. Emisphere's eligen technology makes it possible to orally deliver a therapeutic molecule without altering its chemical form or biological integrity.