A Research Study Looking at How Faster Aspart Injected in Double Concentration Works in the Body of People With Type 1 Diabetes Mellitus

Study Overview
=================
Brief Summary
-----------------
This study is looking at how five different formulations of faster aspart 200 U/mL reach and stay in the blood after injection. The purpose is to find a formulation that behaves similarly to the reference product called faster aspart 100 U/mL (marketed as Fiasp®). The participant will get all five formulations and the reference product. The order in which the participant gets them is decided by chance. The participant will get each medicine once during the study meaning that the participant will get a total of six injections with study medicine. The medicine will be injected under the skin in the stomach. The study will last for about 2 to 21 weeks depending on individual visit schedule. The participant will have nine clinic visits with the study doctor (including the one in which the participant give consent).

Official Title
-----------------
A Trial Investigating the Pharmacokinetic Properties of Five Formulations of Fast-acting Insulin Aspart 200 U/mL in Subjects With Type 1 Diabetes Mellitus

Conditions
-----------------
Diabetes Mellitus, Type 1

Intervention / Treatment
-----------------
* Drug: Faster Aspart 200 U/mL
* Drug: Faster aspart 100 U/mL


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, aged 18-64 years (both inclusive) at the time of signing informed consent Diagnosed with type 1 diabetes mellitus greater than or equal to 1 year prior to the day of screening Treated with multiple daily insulin injections or continuous subcutaneous insulin infusion greater than or equal to 1 year prior to the day of screening Exclusion Criteria: Participation in any clinical trial of an approved or non-approved investigational medicinal product within 90 days before screening in this trial Blood donation, plasma donation or blood draw, defined as any of the below: In excess of 400 mL within the past 90 days prior to the day of screening OR In excess of 50 mL within the past 30 days prior to the day of screening Use of tobacco and nicotine products, defined as any of the below: Smoking more than 1 cigarette or the equivalent per day OR Not able or willing to refrain from smoking and use of nicotine substitute products during the in-house periods

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Participants will be allocated to a treatment sequence consisting of 5 formulations of faster aspart 200 U/mL and faster aspart 100 U/mL in following sequence: formulation D, faster aspart 100 U/mL, formulation B, formulation A, formulation C, formulation E. The dosing visits will be separated by wash-out periods (2-21 days). | Drug: Faster Aspart 200 U/mL<br>* A single dose (0.15 U/kg) of five formulations of fast-acting insulin aspart 200 U/mL (formulations A, B, C, D, E) in a sequential manner via subcutaneous injection.<br>Drug: Faster aspart 100 U/mL<br>* A single dose (0.15 U/kg) of fast-acting insulin aspart 100 U/mL via subcutaneous injection.<br>|
| Experimental: Group B<br>Participants will be allocated to a treatment sequence consisting of 5 formulations of faster aspart 200 U/mL and faster aspart 100 U/mL in following sequence: formulation C, formulation B, formulation D, formulation E, formulation A, faster aspart 100 U/mL. The dosing visits will be separated by wash-out periods (2-21 days). | Drug: Faster Aspart 200 U/mL<br>* A single dose (0.15 U/kg) of five formulations of fast-acting insulin aspart 200 U/mL (formulations A, B, C, D, E) in a sequential manner via subcutaneous injection.<br>Drug: Faster aspart 100 U/mL<br>* A single dose (0.15 U/kg) of fast-acting insulin aspart 100 U/mL via subcutaneous injection.<br>|
| Experimental: Group C<br>Participants will be allocated to a treatment sequence consisting of 5 formulations of faster aspart 200 U/mL and faster aspart 100 U/mL in following sequence: formulation E, formulation C, formulation A, formulation B, faster aspart 100 U/mL, formulation D. The dosing visits will be separated by wash-out periods (2-21 days). | Drug: Faster Aspart 200 U/mL<br>* A single dose (0.15 U/kg) of five formulations of fast-acting insulin aspart 200 U/mL (formulations A, B, C, D, E) in a sequential manner via subcutaneous injection.<br>Drug: Faster aspart 100 U/mL<br>* A single dose (0.15 U/kg) of fast-acting insulin aspart 100 U/mL via subcutaneous injection.<br>|
| Experimental: Group D<br>Participants will be allocated to a treatment sequence consisting of 5 formulations of faster aspart 200 U/mL and faster aspart 100 U/mL in following sequence: formulation A, formulation D, formulation C, faster aspart 100 U/mL, formulation E, formulation B. The dosing visits will be separated by wash-out periods (2-21 days). | Drug: Faster Aspart 200 U/mL<br>* A single dose (0.15 U/kg) of five formulations of fast-acting insulin aspart 200 U/mL (formulations A, B, C, D, E) in a sequential manner via subcutaneous injection.<br>Drug: Faster aspart 100 U/mL<br>* A single dose (0.15 U/kg) of fast-acting insulin aspart 100 U/mL via subcutaneous injection.<br>|
| Experimental: Group E<br>Participants will be allocated to a treatment sequence consisting of 5 formulations of faster aspart 200 U/mL and faster aspart 100 U/mL in following sequence: faster aspart 100 U/mL, formulation A, formulation E, formulation D, formulation B, formulation C. The dosing visits will be separated by wash-out periods (2-21 days). | Drug: Faster Aspart 200 U/mL<br>* A single dose (0.15 U/kg) of five formulations of fast-acting insulin aspart 200 U/mL (formulations A, B, C, D, E) in a sequential manner via subcutaneous injection.<br>Drug: Faster aspart 100 U/mL<br>* A single dose (0.15 U/kg) of fast-acting insulin aspart 100 U/mL via subcutaneous injection.<br>|
| Experimental: Group F<br>Participants will be allocated to a treatment sequence consisting of 5 formulations of faster aspart 200 U/mL and faster aspart 100 U/mL in following sequence: formulation B, formulation E, faster aspart 100 U/mL, formulation C, formulation D, formulation A. The dosing visits will be separated by wash-out periods (2-21 days). | Drug: Faster Aspart 200 U/mL<br>* A single dose (0.15 U/kg) of five formulations of fast-acting insulin aspart 200 U/mL (formulations A, B, C, D, E) in a sequential manner via subcutaneous injection.<br>Drug: Faster aspart 100 U/mL<br>* A single dose (0.15 U/kg) of fast-acting insulin aspart 100 U/mL via subcutaneous injection.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCIAsp,0h-t - Area under the serum insulin aspart concentration-time curve from 0 to t hours after investigational medicinal product (IMP) administration, where t is end of exposure | Measured in pmol*h/L | 0 to 10 hours after IMP administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCIAsp,0-1h - Area under the serum insulin aspart concentration-time curve from 0 to 1 hour after IMP administration | Measured in pmol*h/L | 0 to 1 hour after IMP administration | 
| AUCIAsp,0-2h - Area under the serum insulin aspart concentration-time curve from 0 to 2 hours after IMP administration | Measured in pmol*h/L | 0 to 2 hours after IMP administration | 
| AUCIAsp,0-inf - Area under the serum insulin aspart concentration-time curve from 0 hours after IMP administration to infinity | Measured in pmol*h/L | 0 to 10 hours after IMP administration | 
| Cmax,IAsp - Maximum observed serum insulin aspart concentration | Measured in pmol/L | 0 to 10 hours after IMP administration | 
| tmax,IAsp - Time to maximum observed serum insulin aspart concentration | Measured in minutes | 0 to 10 hours after IMP administration | 
| Number of adverse events in the treatment emergent period | Count of events | 0 to 2 days after IMP administration | 
| Number of local reactions at the injection site in the treatment emergent period | Count of injection site reactions | 0 to 2 days after IMP administration | 
| Number of hypoglycaemic episodes in the treatment emergent period | Count of hypoglycaemic episodes | 0 to 16 hours after IMP administration |