a trial investigating the continuous subcutaneous insulin infusion of a liquid formulation of biochaperone insulin lispro in comparison to humalog®

Conditions: Type 1 Diabetes Mellitus

Summary: this study is constituted of 2 parts: part a: a total of 36 patients will be enrolled in part a. each eligible subject will participate in two 14-day treatment periods with continuous subcutaneous insulin infusion (csii) of biochaperone insulin lispro and insulin lispro (humalog®, eli lilly and company). each treatment period consists of 10 treatment days under free living conditions (e.g. home / workplace) and under standardised conditions at the clinic. various assessments for pharmacodynamics, pharmacokinetics, pump compatibility, short-term efficacy and safety are performed on selected days, including: * mixed meal test (mmt), day 1, day 3, day 12 and day 14, that will assess the post-prandial glucose response for 6 hours after individualized standard meal (fixed nutrient ratio) ingestion and bolus administration via csii. * continuous glucose monitoring (cgm), (day 1 - 14) that will be used in blinded mode (i.e. neither subjects nor the investigators are aware of the sensor glucose values). * pump compatibility (day 1 - 14): subjects will continue csii treatment with the investigational medicinal products (imp) during the outpatient periods. part b: a total of 44 patients will be enrolled. subjects will be randomized to a 4-period cross-over study aiming at comparing the performance of bc lispro and humalog after a prandial bolus administration with two different csii systems (roche accu-chek® spirit and medtronic paradigm® veo™) or with a syringe. pharmacodynamics, pharmacokinetics, pump compatibility and safety will be analyzed. each period will include a mixed meal tolerance test with a csii device and a mixed meal tolerance test with the same dose of insulin administered with a syringe.


Eligibility criteria:
inclusion criteria: * type 1 diabetes for at least 12 months * body mass index (bmi) between 18.5 and 28.5 kg/m\^2, both inclusive * using or having used a roche csii system (accu-chek® spirit combo/ accu- chek® spirit) for at least 6 months before screening. in part b subjects using any form of csii treatment for at least 6 months before screening will be included. * hba1c \<= 9.0%. * total insulin dose of \< 1.2 (i)u/kg/day * ability to calculate insulin bolus manually or using a bolus calculator and willingness to consume regular meals, perform carbohydrate counting, self-monitoring of plasma glucose (smpg) profiles and use of continuous glucose monitoring (cgm). * fasting c-peptide \<= 0.30 nmol/l exclusion criteria: * known or suspected hypersensitivity to investigational medicinal product(s) (imp(s)) or related products * type 2 diabetes mellitus * previous participation in this trial. * receipt of any investigational product in a clinical trial within 60 days before randomisation in this trial * clinically significant abnormal haematology, biochemistry, urinalysis, or coagulation screening test * presence of clinically significant acute gastrointestinal symptoms * known slowing of gastric emptying and or gastrointestinal surgery * unusual meal habits and special dietary requirements or unwillingness to eat the food provided in the trial * history of diabetic ketoacidosis (dka) episodes requiring hospitalization within 6 months prior to screening * history of abscess at the infusion site within 6 months prior to screening * hypoglycaemia unawareness as judged by the investigator * history of severe hypoglycaemic episodes requiring hospitalization within the last 6 months prior to screening