A Multiple Dose Study Investigating Pharmacokinetics and Pharmacodynamics of Subcutaneous NNC0363-0845 in Participants With Type 1 Diabetes Pharmacokinetics and Pharmacodynamics: How Insulin NNC0363-0845 is Transported Throughout the Body and How It Works

Study Overview
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Brief Summary
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This study is designed to investigate the movement of insulin NNC0363-0845 throughout the body and how it works for the treatment of type 1 diabetes mellitus. The aim of the study is to improve clinical outcomes for patients with type 1 diabetes mellitus by better controlling the blood sugar levels. Participants will get insulin NNC0363-0845 as well as insulin detemir (Levemir®). NNC0363-0845 is a new insulin molecule designed to provide blood sugar-dependent insulin action, while insulin detemir is commonly used and prescribed by doctors. Participants will get subcutaneous (under your skin) injections of insulin NNC0363-0845 (study medicine) up to 6 times daily for 3 days, and of insulin detemir up to 6 times daily for another 3 days. Which medication participants receive first and which second, insulin NNC0363-0845 or insulin detemir, is decided by chance. The study will last for about 6 weeks up to a maximum of 14 weeks. Participants will have 2 in-house visits (where participants will stay at the site for 4 nights) and 5 outpatient visits with the study doctor. Participants will have frequent contact with the study doctor during the study. During the in-house visits, two intravenous catheters (a thin tube inserted into a vein) will be inserted for blood sampling and infusions. Interested parties may not participate in the study if the study doctor believes it will affect their health negatively. Women cannot take part if they are of childbearing potential.

Official Title
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A Multiple Dose Study Investigating Pharmacokinetics and Pharmacodynamics of Subcutaneous NNC0363-0845 in Participants With Type 1 Diabetes

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: NNC0363-0845
* Drug: Insulin detemir


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Male participant or female participant of non-childbearing potential. Non-child-bearing potential being defined as surgically sterilised (i.e. documented hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or being postmenopausal (defined as no menses for 12 months without an alternative medical cause) prior to the day of screening. Aged 18-64 years (both inclusive) at the time of signing informed consent. Diagnosed with type 1 diabetes mellitus 1 year or more before screening. Current daily basal insulin treatment greater than 0.2 and below or equal to 0.5 (I)U/kg/day. Current total daily insulin treatment between 0.4 and 0.8 (I)U/kg/day (both inclusive). Body mass index between 18.5-29.9 kg/m^2 (both inclusive). HbA1c (glycated haemoglobin) below or equal to 8.0%. Key exclusion criteria: Male of reproductive age who, or whose female partner(s), is not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice). Adequate contraceptive measures include that the male participant uses a condom during intercourse and that the partner practices adequate contraception (risk of pregnancy must be lower than 1%). In addition, participants must not donate sperm for the duration of the study.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NNC0363-0845 followed by insulin detemir<br>Participants will get subcutaneous (under the skin) injections of insulin NNC0363-0845 (study medicine) up to 6 times daily for 3 days. After a 4-21 days wash-out period with no injections they will get subcutaneous injections of insulin detemir up to 6 times daily for 3 days. | Drug: NNC0363-0845<br>* Participants will receive 0.5 nmol/kg NNC0363-0845 s.c. (subcutaneous - under the skin) every 4 hours up to 6 times daily (i.e. 3 nmol/kg/day) for 3 days The study will last for about 6 weeks up to a maximum of 14 weeks<br>|
| Experimental: Insulin detemir followed by NNC0363-0845<br>Participants will get subcutaneous (under the skin) injections of insulin detemir up to 6 times daily for 3 days. After a 4-21 days wash-out period with no injections they will get subcutaneous injections of NNC0363-0845 (study medicine) up to 6 times daily for 3 days. | Drug: Insulin detemir<br>* Participants will receive 0.083 U/kg insulin detemir s.c. (subcutaneous - under the skin) every 4 hours up to 6 times daily (i.e. 0.5 U/kg/day) for 3 days The study will last for about 6 weeks up to a maximum of 14 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCPG,0.5-2h Area under the plasma glucose-time curve at steady concentrations | messured in h*mmol/L | From 0.5 to 2 hours after initiation of meal glucose appearance test (visit 4 day 3 and visit 5 day 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCPG,0-1h Area under the plasma glucose-time curve at steady concentrations | messured in h*mmol/L | From 0 to 1 hour after initiation of meal glucose appearance test (visit 4 day 3 and visit 5 day 3) | 
| AUCPG,0-2hArea under the plasma glucose-time curve at steady concentrations | messured in h*mmol/L | From 0 to 2 hours after initiation of meal glucose appearance test (visit 4 day 3 and visit 5 day 3) | 
| AUCPG,0-4h Area under the plasma glucose-time curve at steady concentrations | messured in h*mmol/L | From 0 to 4 hours after initiation of meal glucose appearance test (visit 4 day 3 and visit 5 day 3) | 
| ∆PGav,0-1h Mean change in plasma glucose at steady concentrations | messured in mmol/L | From 0 to 1 hour after initiation of meal glucose appearance test (visit 4 day 3 and visit 5 day 3) | 
| ∆PGav,0-2h Mean change in plasma glucose at steady concentrations | messured in mmol/L | From 0 to 2 hours after initiation of meal glucose appearance test (visit 4 day 3 and visit 5 day 3) | 
| Number of adverse events | Number of events | From first IMP administration until 16 hours after last IMP administration (visit 4 day 3 and visit 5 day 3) |