Insulin is normally not bioavailable when taken through the oral route, as degradation of the molecule may occur both in the ventricle and in the intestine. Oral administration with uptake from the lesser intestine would offer major advantages if made possible. It would offer a simple non-injection method to administer insulin in connection with a meal and absorbed insulin would enter the blood stream and mimic the natural distribution in the body with a first pass through the liver. The sponsor of this study has developed a novel oral insulin formulation that is based on a proprietary dextran matrix. The investigational drug is a capsule containing 100 IU of human insulin in dextran matrix. The primary objective of this study is to establish the safety, tolerance and PD profile (i.e. pharmacodynamic parameters for glucose and insulin) of peroral insulin in dextran matrix in patients with type 2 diabetes. The phase I/II study protocol consists of two parts; part 1 (dose finding) and part 2 (dose verification). In study part 1 single escalating doses of oral insulin or placebo is given to the test subjects. Capillary blood glucose is used to assess the insulin effect. Subsequently, in study part 2, the investigational drug will be administered 3 times daily on 6 consecutive days. The starting dose of part 2 will be the lowest effective dose found in study part 1. Dose escalation will be done in increments of 100 IU. The total number of subjects will be 32 (for part 1 and 2 combined).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
32
Fixed dose capsule with 100 IU of insulin in dextran matrix. Investigational drug or placebo are administered in conjunction with food intake on a background of metformin.
Karolinska Trial Alliance, Phase I Unit
Stockholm, Solna, Stockholm, Sweden
Identification of the lowest dose of oral insulin in dextran matrix that produces a significant lowering of post-prandial blood glucose.
Time frame: 6 hours
To establish the dose(s) when administered in a multi-dose fashion that lowers plasma glucose levels versus placebo in patients with Type 2 diabetes
Time frame: 8 days
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