Diabetes Mellitus type 2 MedDRA version: 16.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: DM-199
Product Code: DM-199
Pharmaceutical Form: Solution for injection
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous us
Sponsors
DiaMedica USA Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Status: Parts A and C: healthy subjects Parts B and D: type 2 diabetes mellitus patients 2. Gender: Parts A, B, C and D: males and/or females; in Parts A, B and C, females may be of childbearing or non childbearing potential; in Part D, females must be of non-childbearing potential 3. Age: Parts A and C: 18 - 65 years, inclusive Parts B and D: 18 - 75 years, inclusive 4. BMI: Parts A and C: 18.0 - 30.0 kg/m2 Parts B and D: 25.0 - 35.0 kg/m2 for Part B and 25.0 - 45.0 kg/m2 with a maximum body weight up to 165 kg for Part D; of eligible patients, those with a BMI =27 will preferably be included in order to match the demographics of the typical BMI observed in patients with well characterized type 2 diabetes mellitus in the United States of America 5. For females of non-childbearing potential: females must be either surgically sterilized or at least 1 year postmenopausal (amenorrhoea duration of at least 12 months) and have a negative pregnancy test at screening and each admission 6. For females of childbearing potential: females must be non-pregnant and non lactating, and have a negative serum pregnancy test at screening and each admission. 7. For females of child-bearing potential: willingness to use adequate contraception from screening until 90 days after the follow up visit. Adequate contraception is defined as using hormonal contraceptives combined with at least 1 of the following forms of contraception: an intrauterine device, a diaphragm or cervical cap, or a condom 8. For males: willingness to use adequate contraception from entry in the clinical research center until 90 days after the follow-up visit 9. Ability and willingness to abstain from alcohol, methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, "powerdrinks"), grapefruit (juice) and tobacco products from 48 hours prior to entry in the clinical research center until discharge each period 10. Medical history without clinically significant abnormalities 11. Parts A and C: Resting supine blood pressure of 140/90 mmHg or lower and higher than 90/50 mmHg, and showing no clinically relevant deviations as judged by the Principal Investigator 12. Parts B and D: Resting supine blood pressure of 160/100 mmHg or lower and higher than 90/50 mmHg, and showing no clinically relevant deviations as judged by the Principal Investigator 13. Computerised (12-lead) ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the Principal Investigator 14. All values for hematology and for clinical chemistry tests of blood and urine within the normal range or showing no clinically relevant deviations as judged by the Principal Investigator. 15. Willing to sign the written Informed Consent Form (ICF Additional Inclusion Criteria Specific to Type 2 Diabetes Mellitus Patients (Part B and Part D) ++ Diagnosed with type 2 diabetes mellitus ++ 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. Non-systemic steroids are permitted ++ The use (before and in the same dose during the study) of antihypertensives, (except angiotensin-converting-enzyme (ACE) inhibitors) and drugs to treat dyslipidaemia
Exclusion criteria
Exclusion criteria: 1. Evidence of clinically relevant pathology 2. Mental handicap 3. History of relevant drug and/or food allergies 4. Smoking more than 5 cigarettes, 1 cigar or 1 pipe daily 5. Parts A to C: History of alcohol abuse or drug addiction (including soft drugs like cannabis products) Part D: history of drug addiction (including soft drugs like cannabis products); history of alcohol abuse within the year prior to the start of the study 6. Use of concomitant medication, except for acetaminophen (paracetamol), which is allowed up to 3 days before entry into the clinical research centre (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. 7. 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) 8. Donation or blood loss of more than 50 mL of blood within 60 days prior to drug administration. Donation of more than 1.5 litres of blood (for men) / more than 1.0 litres of blood (for women) in the 10 months preceding the start of this study. 9. Positive drug screen (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants and alcohol) 10. 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) 11. Positive screen on HBsAg, anti-HCV or anti-HIV 1/2 12. Illness within 7 days prior to (the first) drug administration 13. Serum creatinine > upper limit of the normal (ULN) range Additional Exclusion Criteria Specific to Type 2 Diabetes Mellitus Patients (Part B and Part D) 14. The use of insulin and thiazolidinediones for type 2 diabetes mellitus 3 months prior to screening is not allowed. 15. History of diabetic ketoacidosis or hyperosmolar coma 16. Advanced diabetic complications, including neuropathy, nephropathy, retinopathy or other symptoms
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to evaluate the safety and tolerability of single and multiple subcutaneous doses of DM 199 in healthy subjects and type 2 diabetes mellitus patients to determine the plasma pharmacokinetic profile of DM-199 after administration of single and multiple doses of DM-199 in healthy subjects and type 2 diabetes mellitus patients ;Secondary Objective: to determine the effect of DM-199 on glucose homeostasis (via fasting glucose, fasting insuline and HbA1c levels), standardized meal tolerance test, C-peptide, fructosamine, GLP-1, glucagon, adiponectin, aldosterone, renin and lipids measurements, and homeostatic model assessment of insulin resistance/ beta cell function (HOMA) determination in type 2 diabetes mellitus patients to assess the formation of antibodies to DM-199 after administration of multiple doses of DM-199 in healthy subjects and type 2 diabetes mellitus patients to determine changes in immune cell populations by fluorescence-activated cell sorting analysis following multiple doses of DM-199 in healthy subjects and type 2 diabetes mellitus patients ;Primary end point(s): Safety: Parts A, B, C and D: adverse events, vital signs (including supine and standing systolic and diastolic blood pressure, pulse, body temperature, respiratory rate), 12-lead ECG, clinical laboratory (including clinical chemistry, hematology, coagulation and urinalysis) tests, local tolerability at injection site and physical examination : Part A: fasting and non-fasting serum glucose : Parts B, C and D: fasting glucose using the glucometer (or determined by the clinical laboratory for Part D patients only when they are in the clinic) : Parts C and D: anti-drug antibodies (ADA) PK : Parts A, B, C and D: plasma concentrations of DM-199 and PK parameters ;Timepoint(s) of evaluation of this end point: For the different parts (A, B, C and D) of the study the primary end points will be scheduled at different timepoints according to Amended Protocol Version 4.0 dated | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PD: Parts B and C: glucose (fasting and non-fasting), insulin, C-peptide, glucagon and GLP-1 (active and total); in Part B these will be measured as a response to a meal tolerance test (MTT) : Parts C and D: analysis of immune cell populations (lymphocytes, B lymphocytes, T (helper/cytotoxic) lymphocytes, monocytes and natural killer cells) : Part D: adiponectin, aldosterone, renin and lipid (total cholesterol, high density lipoprotein [HDL], low density lipoprotein [LDL], free fatty acids, triglycerides) concentrations POC: Part D: glucose (fasting and non-fasting), insulin, C-peptide, glucagon and GLP-1 (active and total) as a response to an MTT, fasting glucose using the glucometer (or determined by the clinical laboratory for Part D patients only when they are in the clinic), fasting insulin, fasting insuline, fructosamine and HbA1c ;Timepoint(s) of evaluation of this end point: For the different parts (A, B, C and D) of the study the secondary end points will be scheduled at different timepoints according to Amended Protocol Version 4.0 dated 07NOV13 throughout the study. | — |
Countries
Netherlands
Contacts
Public ContactProject Associate/Suzanne Harms
PRA
Outcome results
None listed