A Study to Evaluate the Safety and Effectiveness of DM199 in Healthy Subjects and Type 2 Diabetes Patients

This is an interventional treatment trial for Diabetes Type 2 focused on measuring type 2 diabetes, diabetes mellitus, type 2 diabetes mellitus, HbA1c, blood glucose, glucose control, DiaMedica, DM-199, DM199, recombinant human tissue kallikrein-1, tissue kallikrein-1 Read More

Inclusion Criteria:

1. Status : Parts A and C: healthy subjects

   • Parts B and D: type 2 diabetes mellitus patients :

2. Body Mass Index : Parts A and C: 18.0 - 30.0 kg/m2

   • Parts B and D: 25.0 - 35.0 kg/m2
3. HbA1c : Parts B and D: at screening between 6.5% and 9.0%, inclusive for patients using one oral anti-diabetic medication, and between 6.0% and 8.5%, inclusive for patients using two or more oral anti-diabetic medications
4. Fasting blood glucose : Parts B and D: within 7.5-13.5 mmol/L, inclusive at entry into the clinical research center (Day -1 for Part B or Day -2 for Part D)
5. Women of childbearing potential agree to use an appropriate contraceptive method (hormonal, IUD, or diaphragm) until 90 days after the follow-up visit. For males: willingness to use adequate contraception from entry in the clinical research center until 90 days after the follow-up visit
6. Medical history without clinically significant abnormalities
7. Parts B and D: Taking a stable dose of one or more oral anti-diabetic medications, such as metformin, sulphonylurea or any other orally administered glucose lowering medication (except for thiazolidinediones) for at least 3 months prior to screening. Receiving no other chronic medications, including dietary supplements, that alter blood glucose control.
8. Parts A and C: Resting supine blood pressure of 140/90 mmHg or lower and higher than 90/50mmHg at screening, and showing no clinically relevant deviations as judged by the Principal Investigator
9. Parts B and D: Resting supine blood pressure of 160/100 mmHg or lower and higher than 90/50mmHg at screening, and showing no clinically relevant deviations as judged by the Principal Investigator

Exclusion Criteria:

1. Evidence of clinically relevant pathology
2. Pregnancy or lactation
3. For healthy volunteers: use of concomitant medication, except for acetaminophen (paracetamol), which is allowed up to 3 days before entry into the clinical research center (after that time the use of a limited amount of acetaminophen is permitted after consultation with the Principal Investigator). Multivitamins and vitamin C are allowed up to 7 days before entry into the clinical research center. All other medication (including over the counter medication, health supplements, and herbal remedies such as St. John's Wort extract) must have been stopped at least 14 days prior to entry into the clinical research center.
4. Participation in a drug study within 60 days prior to drug administration. Participation in more than 3 other drug studies (for men) / more than 2 other drug studies (for women) in the 10 months preceding the start of this study)
5. Positive drug screen (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants and alcohol)
6. Intake of more than 24 units of alcohol per week (one unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits)
7. Positive screen on HBsAg, anti-HCV or anti-HIV 1/2
8. Illness within 7 days prior to (the first) drug administration

9. Serum creatinine > upper limit of the normal (ULN) range

   Additional Exclusion Criteria Specific to Type 2 Diabetes Mellitus Patients (Part B and Part D)

10. The use of insulin and thiazolidinediones for type 2 diabetes mellitus 3 months prior to screening is not allowed.
11. The use of angiotensin converting enzyme (ACE) inhibitors 1 month prior to screening is not allowed.
12. History of diabetic ketoacidosis or hyperosmolar coma
13. Advanced diabetic complications, including neuropathy, nephropathy, retinopathy or other symptoms