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

• Status: Completed
• Trial end date: 2014-11-01
• Target enrollment: 0
• Participant gender: All

Summary

DM199 (recombinant human tissue kallikrein-1) is a new investigational compound that may eventually be used for the treatment of Diabetes Mellitus Type 2. This is the first time that this compound is being given to humans.

The purpose of the study is to investigate to what extent DM199 is safe and tolerated. Further, it will be investigated how quickly and to what extent DM99 is absorbed and eliminated from the body (this is called pharmacokinetics). In addition, the effect of the compound on the body will be investigated (this is called pharmacodynamics).

This study is not intended to improve anyone's health, but is necessary for the further development of DM199.

The study consists of 4 parts. Each part (A, B, C and D) will consist of one or several periods. The research will be conducted in healthy male and female volunteers (Part A and C) and in male and female type 2 diabetes mellitus patients (Part B and D).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: DiaMedica Therapeutics Inc; DiaMedica USA Inc.
• Treatments: Kallikreins

Criteria

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