Capsulin™ OAD (oral anti-diabetic)

Diabetology has developed a novel oral formulation of insulin using its in-licensed Axcess™ drug delivery system. This delivery system uses no NCE’s and has been shown to be effective at oral delivery of peptides in multiple studies in man and animal models, using not only insulin but also calcitonin and parathyroid hormone (PTH).

Oral insulin has many potential advantages over other forms of insulin dellivery, as it most closely mimics the natural insulin secretion pathway from the pancreas to the liver. By delivering insulin to the liver as the oral route does, the main organ of glucose regulation is solicited, and insulin side-effects in the peripheral circulation (from other routes of administration) may be avoided.

Study Results

Phase II study in type 2 diabetes recently completed

(results coming shortly)

Phase I study

The first clinical study of Capsulin was completed in the UK in April 2005 in healthy volunteers to investigate and measure the effect of orally administering insulin in the Axcess formulation on blood glucose, c-peptide and circulating insulin levels in healthy subjects. The study was open label and sequential; although there was no blinding in the study, the parameters being examined in the study were derived from blood and subjective bias in the data collected was thus minimised. The main conclusions of the study are as follows:

• Capsulin was well tolerated by the volunteers;
• Capsulin shows evidence of bioavailability and was biologically active in humans (fall in blood glucose levels and suppression of C-peptide levels);
• There was a marked non-linear relationship between plasma insulin levels in the two naso-jejeunal groups suggesting that the 170iu dose may be >90% bound by the liver insulin receptors with minimal overspill of insulin into the circulation, whereas the 340iu dose floods the liver and spills over into plasma (10 times the plasma levels with 170iu).

This graph, from the phase I trial, illustrates the elevation in plasma insulin levels of healthy subjects following administration of 170iu Capsulin™.This allowed us to green light the progression of the development project into phase II.

Strong pre-clinical study results

Diabetology has studied its novel oral insulin formulations in multiple animal model systems including rats, juvenile pigs, primates and diabetic dogs. Results demonstrate:

1. Successful insulin absorption through the intestine;
2. Consistent 6-10% bioequivalence as assessed by impact upon blood glucose concentration relative to injected insulin;
3. No chemical interaction between insulin and the carrier formulation;
4. No unexpected toxicity or safety issues; and
5. Predictable onset of activity.

Background on Diabetes & Insulin

• 171 million people with diabetes in 2000
• 366 million people with diabetes by 2030
• Incidence is set to more than double in the next 25 years
• Global epidemic resulting from the spread of the “western lifestyle”
• Diabetes causes about 5% of all deaths globally each year

The inexorable spread of the western lifestyle across the world is precipitating a diabetes epidemic. Diabetes is the most common human endocrine disease and the term covers a group of metabolic disorders whose central feature is elevated blood glucose, or hyperglycemia. Sustained hyperglycemia results in the deterioration of multiple tissue types, particularly vascular tissues, and may eventually lead to kidney failure, cardiovascular disease, leg ulcers, stroke, neuropathy and retinopathy. In 2002 it was estimated that the direct and indirect cost of diabetes was $132 billion annually in the US alone.

The principal regulator of blood glucose concentration is insulin, a hormone synthesized by the ß islet cells of the pancreas and secreted in response to elevated blood glucose levels. Insulin increases the uptake of glucose by multiple tissues, promotes its utilization as an energy source, reduces the production of new glucose, and slows down the production and release of alternative energy sources such as fatty acids. Its principal target organs are the liver, skeletal muscle and fat tissue. In particular, the liver plays a central role in maintaining blood glucose concentration within normal limits since it is both a major point of glucose uptake when blood levels of the substance rise and the primary source of glucose production to counter low blood glucose levels (hypoglycaemia).

Publications

Poster presented at ADA 2005:

Absorption of Orally Ingested Insulin in Human Type 1 Diabetic Subjects:Proof of Concept Study

Click Here for Details (pdf)

Poster presented at ADA 2004:

Early Evaluation of a Novel Oral Insulin Delivery System in Healthy Volunteers

Click Here for Details (pdf)