A Study to Look at How Safe NNC0472-0147 is in Healthy People and in People With Type 2 Diabetes

Study Overview
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Brief Summary
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This study is investigating the safety and tolerability of the new medicine NNC0472-0147, its concentrations in the blood and its effect on blood sugar for the treatment of diabetes. Another goal of the study is to determine an effect of NNC0472-0147 on cholesterol. The first part of the study is conducted in healthy people, while the second part involves people with type 2 diabetes (T2DM). The study will test how NNC0472-0147 is tolerated by the body, how it is taken up in the blood, how long it stays there and how much blood sugar is lowered. In part 1, participants will either get the new medicine NNC0472-0147 or placebo (an injection that does not contain active medicine) - which treatment is decided by chance. In part 2, participants will either get the new medicine NNC0472-0147 or insulin glargine - which treatment is decided by chance. It is the first time that NNC0472-0147 is tested in humans. Participants will get once daily injections of either NNC0472-0147 or insulin glargine for a treatment period of fourteen days. The injections will be given under the skin (subcutaneously, s.c.) of the left thigh. Participants will be in the study for about 7 weeks. There will be 15 visits with the study doctor. People cannot be in the study if the study doctor thinks that there are risks for their health. Only women who cannot become pregnant are allowed to participate.

Official Title
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A Trial Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneous NNC0472-0147 in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus

Conditions
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Healthy Volunteers, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: NNC0472-0147
* Drug: insulin glargine
* Drug: Placebo (NNC0472-0147)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1: Male Aged 18-55 years (both inclusive) at the time of signing nformed consent. Part 2: Male, or female of non-child bearing potential. Non-child bearing potential is defined by being surgically sterilised (documented hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or being postmenopausal (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 T2DM at least 180 days prior to the day of screening. Treated with any insulin for 90 days or longer prior to the day of screening. Low-density lipoprotein cholesterol level above 1.80 mmol L. Exclusion Criteria: Part 1: - Male of reproductive age who or whose partner(s) is not using highly effective contraceptive methods (highly effective contraceptive measures as required by local regulation or practice). Highly effective contraceptive measures include that the male subject uses a condom during intercourse and that the partner practices highly effective contraception (risk of pregnancy must be lower than 1%). In addition, subjects must not donate sperm for the duration of the trial. Part 2: Male of reproductive age who or whose partner(s) is not using highly effective contraceptive methods (highly effective contraceptive measures as required by local regulation or practice). Highly effective contraceptive measures include that the male subject uses a condom during intercourse and that the partner practices highly effective contraception (risk of pregnancy must be lower than 1%). In addition, subjects must not donate sperm for the duration of the trial. Use of oral antidiabetic drugs (OADs) other than metformin or use of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. exenatide, liraglutide, semaglutide) within 90 days prior to the day of screening. Treatment with peptide proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors within 180 days prior to the day of screening.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part 1: Single ascending dose, placebo control. Part 2: Multiple ascending dose design, active control.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NNC0472-0147 Part 1<br>Part 1: Each cohort will consist of 8 healthy subjects - 6 subjects will receive a single subcutaneous (s.c., under the skin) dose of NNC0472-0147. | Drug: NNC0472-0147<br>* Part 1: A single dose of NNC0472-0147, dose increased in each cohort. Part 2: Daily doses of NNC0472-0147, dose increased in each cohort.<br>|
| Placebo Comparator: Placebo Part 1<br>Part 1: Each cohort will consist of 8 healthy subjects - 2 subjects will receive a single s.c. dose of placebo. | Drug: Placebo (NNC0472-0147)<br>* Part 1: A single dose of placebo, dose increased in each cohort.<br>|
| Experimental: NNC0472-0147 Part 2<br>Part 2: Each cohort will consist of 12 subjects with T2DM. 9 subjects will receive once daily s.c. doses of NNC0472-0147 for 14 days | Drug: NNC0472-0147<br>* Part 1: A single dose of NNC0472-0147, dose increased in each cohort. Part 2: Daily doses of NNC0472-0147, dose increased in each cohort.<br>|
| Active Comparator: Insulin glargine Part 2<br>Part 2: Each cohort will consist of 12 subjects with T2DM - 3 subjects will receive once daily s.c. doses of insulin glargine for 14 days. | Drug: insulin glargine<br>* Part 2: A fixed dose level of 0.5 U/kg insulin glargine will be used in all cohorts.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of treatment emergent adverse events | Number of events | From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 15, visit 6) | 
| Part 2: Number of treatment emergent adverse events | Number of events | From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 30, visit 14) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of hypoglycaemic episodes of alert value (level 1) below 3.9 mmol/L (70 mg/dL) and equal to or above 3.0 mmol/L (54 mg/dL) | Number of episodes | From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 15, visit 6) | 
| Number of hypoglycaemic episodes of alert value (level 1) below 3.9 mmol/L (70 mg/dL) and equal to or above 3.0 mmol/L (54 mg/dL) | Number of episodes | From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 30, visit 14) | 
| Number of clinically significant hypoglycaemic episodes (level 2) below 3.0 mmol/L (54 mg/dL) | Number of episodes | From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 15, visit 6) | 
| Number of clinically significant hypoglycaemic episodes (level 2) below 3.0 mmol/L (54 mg/dL) | Number of episodes | From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 30, visit 14) | 
| Number of severe hypoglycaemic episodes (level 3) | Number of episodes | From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 15, visit 6) | 
| Number of severe hypoglycaemic episodes (level 3) | Number of episodes | From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 30, visit 14) | 
| Area under the serum NNC0472-0147 concentration-time curve after a single dose | pmol*h/L | From 0 hours until infinity after a single IMP administration at day 1 (visit 2). | 
| Maximum observed serum NNC0472-0147 concentration after a single dose | pmol/L | From 0 hours until last measurement time after a single IMP administration at day 1 (visit 2) | 
| Area under the serum NNC0472-0147 concentration-time curve during one dosing interval at steady state | pmol*h/L | From 0 to 24 hours after last multiple IMP administration at day 14 (visit 9) | 
| Maximum observed serum NNC0472-0147 concentration at steady state | pmol/L | From 0 to 24 hours after last multiple IMP administration at day 14 (visit 9) |