A First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM12470

Study Overview
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Brief Summary
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The purpose of this study is to investigate safety, tolerability, pharmacokinetics (PK) ad pharmacodynamics (PD) of HM12470 after single injection in T1DM and T2DM patients.

Detailed Description
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This study is designed to evaluate safety, tolerability, PK and PD of HM12470 after single administration in subjects with T1DM and T2DM. In some cohorts for this study, the safety, tolerability, PK and PD of HM12470 will be compared with that of commercially available insulin.

Official Title
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A First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single Administration of HM12470 in Subjects With Type 1 (T1DM) and Type 2 Diabetes Mellitus (T2DM)

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Biological: HM12470
* Biological: Active comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for T1DM: T2DM more than 12 monthM Age ≥18 and ≤70 years Body mass index between 18.0 and 35.0 kg/m2 inclusive. Considered generally healthy upon completion of medical history, physical examination and biochemical investigations as judged by the Investigator. Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or post-menopausal for >12 months. Males must be surgically sterile, abstinent or if engaged in sexual relations of child-bearing potential, the subject must be using an acceptable contraceptive method during and for during a period of 60 days after the last dose of Study Drug. Signed and dated informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject). Inclusion Criteria for T2DM: T1DM more than 12 monthM Age ≥18 and ≤70 years Body mass index between 18.0 and 30.0 kg/m2 inclusive. Considered generally healthy upon completion of medical history, physical examination and biochemical investigations as judged by the Investigator. Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or post-menopausal for >12 months. Males must be surgically sterile, abstinent or if engaged in sexual relations of child-bearing potential, the subject must be using an acceptable contraceptive method during and for during a period of 60 days after the last dose of Study Drug. Signed and dated informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject). Exclusion Criteria A subject who has proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator Recurrent major hypoglycemia or hypoglycemic unawareness or recent ketoacidosis pregnant or lactating women participation in an investigational study within 30 days prior to dosing Clinically significant abnormal ECG at screening, as judged by the Investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Very low dose of HM12470 (single dose, subcutaneous injection) | Biological: HM12470<br>* Single dose subcutaneous administration ranging from a very low dose to high dose<br>|
| Experimental: Cohort 2<br>Low dose of HM12470 (single dose, subcutaneous injection) | Biological: HM12470<br>* Single dose subcutaneous administration ranging from a very low dose to high dose<br>|
| Experimental: Cohort 3<br>Intermediate dose of HM12470 (single dose, subcutaneous injection) | Biological: HM12470<br>* Single dose subcutaneous administration ranging from a very low dose to high dose<br>|
| Experimental: Cohort 4<br>High dose of HM12470 (single dose, subcutaneous injection) | Biological: HM12470<br>* Single dose subcutaneous administration ranging from a very low dose to high dose<br>|
| Experimental: Cohort 5<br>Active comparator and a selected dose of HM12470 (single dose, subcutaneous injection) | Biological: HM12470<br>* Single dose subcutaneous administration ranging from a very low dose to high dose<br>Biological: Active comparator<br>* Single dose subcutaneous administration of active comparator<br>|
| Experimental: Cohort 6<br>Active comparator and a selected dose of HM12470 (single dose, subcutaneous injection) | Biological: HM12470<br>* Single dose subcutaneous administration ranging from a very low dose to high dose<br>Biological: Active comparator<br>* Single dose subcutaneous administration of active comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment emergent adverse events |  | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration(Cmax) of HM12470 following a single dose | Pharmacokinetic properties of HM12470 following a single dose will be assessed in plasma using a validated assay | 1 month | 
| Area under the concentration-time curve (AUC) of HM12470 following a single dose | Pharmacokinetic properties of HM12470 following a single dose will be assessed in plasma using a validated assay | 1 month |