| Outcome Measures: |
Primary: Adverse events (AEs), Number of patients with Adverse Events (Part I), Between screening (up to Day -21) and End of study ( up to Day 6)|Laboratory safety parameters, Number of patients with clinically significant changes in Laboratory safety parameters (Part I), Between screening (up to Day -21) and End of study ( up to Day 6)|Physical examination, Number of patients with clinically significant changes in Physical examination (Part I), Between screening (up to Day -21) and End of study ( up to Day 6)|Vital signs, clinically, Number of patients with clinically significant changes in Vital signs (Part I), Between screening (up to Day -21) and End of study ( up to Day 6)|Hypoglycaemic events, Number of patients with Hypoglycaemia events (Part I), Between screening (up to Day -21) and End of study ( up to Day 6)|Hyperglycaemia events, Number of patients with Hyperglycaemia events (Part I), Between screening (up to Day -21) and End of study ( up to Day 6)|Electrocardiograms, Number of patients with clinically significant changes in Electrocardiogram (ECG) (Part I), Between screening (up to Day -21) and End of Treatment ( up to Day 6)|Adverse events (AEs), Number of patients with Adverse Events (Part II), Day of screening to Day 20 (Diary) and During follow up Via (Telephone)|Hypoglycaemic events, Number of patients with Hypoglycaemia events (Part II), Day of screening to Day 20 (Diary) and During follow up Via (Telephone)|Hyperglycaemia events, Number of patients with Hyperglycaemia events (Part II), Day of Run-in to Day 20 (Diary) and During follow up Via (Telephone)|Laboratory safety parameters, Number of patients with clinically significant changes in Laboratory safety parameters (Part II), Day of screening and Day 20|Physical examination, Number of patients with clinically significant changes in Physical examination (Part II), Day of screening, Dosing day 1 and Day 20|Vital signs, Number of patients with clinically significant changes in Vital signs (Part II), Day of screening, Day1-6 and Day 20)|Electrocardiograms, Number of patients with clinically significant changes in Electrocardiogram (ECG) (Part II), Day of screening and Day 20|Anti-insulin Tregopil antibodies, Change in antibody levels (Part II), Day -1 and Day 20 | Secondary: Pharmacokinetics (PK) endpoint-Area under the insulin concentration curve(AUCins)., Area under the insulin concentration curve (Part I), 0 to 1 hour|PK endpoint-Area under the insulin concentration curve(AUCins)., Area under the insulin concentration curve (Part 1), 0 to 2 hour|PK endpoint-Area under the insulin concentration curve(AUCins)., Area under the insulin concentration curve (Part I), 0 to 3 hour|PK endpoint-Area under the insulin concentration curve(AUCins)., Area under the insulin concentration curve (Part I), 0 to 4 hour|PK endpoint-Area under the insulin concentration curve(AUCins)., Area under from time zero to the last measurable concentration sampling time (Part I), Time zero to the last measurable concentration (6 hours)|PK endpoint-Area under the insulin concentration curve(AUCins)., AUC from time zero to infinity (Part I), Day 1, Day 2, Day 6|PK endpoint-time to maximum observed insulin concentration (tmax), Time to maximum observed insulin concentration (Part I), Day 1, Day 2, Day 6|PK endpoint-terminal elimination half-life calculated, Terminal elimination half-life calculated as t½=ln2/ λz (Part I), Day 1, Day 2, Day 6|PK endpoint-Area under the insulin concentration curve in the intended dosing interval (AUCins), Area under the insulin concentration curve in the intended dosing interval (Part I), Day 1, Day 2, Day 6|PK endpoint-Insulin concentration at the end of treatment (Ctrough), Insulin concentration at the end of treatment (Part I), Day 1, Day 2, Day 6|PK endpoint-Insulin concentration in plasma, tlag (lag time), Time to first appearance of insulin concentration in plasma after dosing (Part I), Day 1, Day 2, Day 6|pharmacodynamics (PD) Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals on Day 1, 2 and 6 mixed meal tests, Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (Part I), 0-1 hour|PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals, Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (Part I), 0-2 hour|PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals, Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (Part I), 0-3 hour|PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals, Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (Part I), -10 min-6 hour|PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals, Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (Part I), 0-6 hour|PD Endpoints-Area under the plasma glucose concentration curve in the indicated time intervals, Area under the plasma glucose concentration curve in the indicated time intervals (Part I), 0-1 hour|PD Endpoints-Area under the plasma glucose concentration curve in the indicated time intervals, Area under the plasma glucose concentration curve in the indicated time intervals (Part I), 0-2 hour|PD Endpoints-Area under the plasma glucose concentration curve in the indicated time intervals, Area under the plasma glucose concentration curve in the indicated time intervals (Part I), 0-3 hour|PD Endpoints-Area under the plasma glucose concentration curve in the indicated time intervals, Area under the plasma glucose concentration curve in the indicated time intervals (Part I), 0-4 hour|PD Endpoints-Area under the plasma glucose concentration curve in the indicated time intervals, Area under the plasma glucose concentration curve in the indicated time intervals (Part I), 0-6 hour|PD Endpoints-minimum plasma glucose concentration in the indicated time intervals, Minimum plasma glucose concentration in the indicated time intervals (Part I), 0-1 hour|PD Endpoints-minimum plasma glucose concentration in the indicated time intervals, Minimum plasma glucose concentration in the indicated time intervals (Part I), 0-2 hour|PD Endpoints-minimum plasma glucose concentration in the indicated time intervals, Minimum plasma glucose concentration in the indicated time intervals (Part I), 0-3 hour|PD Endpoints-minimum plasma glucose concentration in the indicated time intervals, Minimum plasma glucose concentration in the indicated time intervals (Part I), 0-4 hour|PD Endpoints-minimum plasma glucose concentration in the indicated time intervals, Minimum plasma glucose concentration in the indicated time intervals (Part I), 0-6 hour|PD Endpoints-maximal plasma glucose concentration in the indicated time intervals, Maximal plasma glucose concentration in the indicated time intervals (Part I), 0-2 hour|PD Endpoints-maximal plasma glucose concentration in the indicated time intervals, Maximal plasma glucose concentration in the indicated time intervals (Part I), 0-4 hour|PD Endpoints-maximal plasma glucose concentration in the indicated time intervals, Maximal plasma glucose concentration in the indicated time intervals (Part I), 0-6 hour|PD Endpoints-maximal plasma glucose observed sampling period, maximal plasma glucose observed sampling period (Part I), -10 min-6 hour|PD Endpoints- ΔGmin minimum postprandial plasma glucose increment, absolute and percent, Minimum postprandial plasma glucose increment, absolute and percent (Part I), 0-6 hour|PD Endpoints- time to onset of action; time to decrease in PG of 5 mg/dL from baseline, Onset of action; time to decrease in PG of 5 mg/dL from baseline (Part I), 0 hour|Duration of action;, time from onset of action to increase in PG ≥ 180 mg/dL post meal or time to increase to baseline PG if baseline \> 180 mg/dL (Part I), 0- 6 hour|Continuous glucose monitoring (CGM) profile, daily glycaemic control assessed d by mean (SD) glucose levels, percentage of time in normal range \[70-180 mg/dL\], percentage of time in hyperglycaemia range \[\>180 mg/dL\], percentage of time in hypoglycaemic range (\<70 mg/dL), percentage of readings in the range of 70-180 mg/dL (3.9- 10.0 mmol/L) per unit of time (Part I), 6 days|PK Endpoints- Maximum concentration recorded ( Day 1, 2,3,4,5,6,20), Maximum concentration recorded (Cmax) (Part II), 0-4 hours|PK Endpoints-Area under the insulin concentration curve ( Day 1, 2,3,4,5,6,20), Area under the insulin concentration curve (AUC) (Part II), 0-1 hours|PK Endpoints-Area under the insulin concentration curve ( Day 1, 2,3,4,5,6,20), Area under the insulin concentration curve (AUC) (Part II), 0-2 hours|PK Endpoints-Area under the insulin concentration curve ( Day 1, 2,3,4,5,6,20), Area under the insulin concentration curve (AUC) (Part II), 0-4 hours|PK Endpoints-Area under the insulin concentration curve ( Day 1, 2,3,4,5,6,20), Area under the insulin concentration curve (aspart) (AUC) (Part II), 0-6 hours|PK Endpoints-Area under the insulin concentration curve ( Day 1, 2,3,4,5,6,20), Area under the insulin concentration curve (AUC) (Part II), 0-last|PK Endpoints-Area under the insulin concentration curve ( Day 1, 2,3,4,5,6,20), Area under the insulin concentration curve (AUC) (Part II), 0-∞|PK Endpoints- terminal elimination half-life calculated ( Day 1, 2,3,4,5,6,20), Terminal elimination half-life calculated as t½=ln2/ λz (Part II), Day 1, Day 2,Day 3,Day 4, Day5, Day 6, Day 20|PK endpoint-time to maximum observed insulin concentration (tmax) ( Day 1, 2,3,4,5,6,20), Time to maximum observed insulin concentration (Part II), Day 1, Day 2,Day 3,Day 4, Day5, Day 6, Day 20|PK Endpoints-Area under the insulin concentration curve ( Day 1, 2,3,4,5,6, 20), Area under the insulin concentration curve (AUC) (Part II), Day 1, Day 2,Day 3,Day 4, Day5, Day 6, Day 20|PK endpoint-Insulin concentration at the end of treatment ( Day 1, 2,3,4,5,6, 20), Insulin concentration at the end of treatment (Ctrough) (Part II), Day 1, Day 2,Day 3,Day 4, Day5, Day 6, Day 20|PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals ( Day 1, 2,3,4,5,6, 20), Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (GExc) (Part II), 0-1 hours|PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals ( Day 1, 2,3,4,5,6, 20), Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (GExc) (Part II), 0-2 hours|PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals ( Day 1, 2,3,4,5,6, 20), Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (GExc) (Part II), 0-3 hours|PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals ( Day 1, 2,3,4,5,6, 20), Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (GExc) (Part II), 0-4 hours|PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals ( Day 1, 2,3,4,5,6,20), Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (GExc) (Part II), 0-6 hours|PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals ( Day 1, 2,3,4,5,6, 20), Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (GAUC) (Part II), 0-1 hours|PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals ( Day 1, 2,3,4,5,6, 20), Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (GAUC) (Part II), 0-3 hours|PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals ( Day 1, 2,3,4,5,6, 20), Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (GAUC) (Part II), 0-4 hours|PD Endpoints-minimum plasma glucose concentration in the indicated time intervals ( Day 1, 2,3,4,5,6, 20), Minimum plasma glucose concentration in the indicated time intervals (Gmin) (Part II), 0-1 hours|PD Endpoints-minimum plasma glucose concentration in the indicated time intervals ( Day 1, 2,3,4,5,6,20), Minimum plasma glucose concentration in the indicated time intervals (Gmin) (Part II), 0-3 hours|PD Endpoints-minimum plasma glucose concentration in the indicated time intervals ( Day 1, 2,3,4,5,6, 20), Minimum plasma glucose concentration in the indicated time intervals (Gmin) (Part II), 0-4 hours|PD Endpoints-maximal plasma glucose concentration in the indicated time intervals ( Day 1, 2,3,4,5,6, 20), Maximal plasma glucose concentration in the indicated time intervals (Gmax) (Part II), 0-4 hours|PD Endpoints -minimal PG concentration in observed sampling period ( Day 1, 2,3,4,5,6, 20), minimal PG concentration in observed sampling period (Part II), 0 - 6 hours|PD Endpoints - maximal PG concentration in observed sampling period ( Day 1, 2,3,4,5,6, 20), maximal PG concentration in observed sampling period (Part II), 0 - 6 hours|PD Endpoints - CGM profile, CGM profile, Day 1 to 20
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