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

NCT01845064 | Completed Phase 1 DMC

• 2 other identifiers: DMA-Clin-199-2013-0012013-000225-30
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Diabetes Type 2

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of single and multiple subcutaneous doses of DM199

  Number of participants with adverse events in the single and multiple ascending dose studies.

  Up to 13 days after final dose

• Determine the pharmacokinetic of DM199 after single and multiple doses

  Determine the plasma pharmacokinetic profile of DM199 after administration of single and multiple doses of DM199 in healthy subjects and type 2 diabetes mellitus patients. Measure plasma DM199 levels in individual participants.

  Up to 3 days after final dose

Secondary Outcomes (3)

• Determine the effect of DM199 on glucose homeostasis in healthy volunteers and type 2 diabetes mellitus patients

  Part C, Day -1 and 14; Part D, Days -1, 14 and 28

• Assess formation of ADA to DM199

  Part C, Day -1 and 42; Part D, Day -1 and 35

• Determine changes in immune cell populations by FACS analysis.

  Part C, Day -1 and 15; Part D, Day -1 and 29

Study Arms (8)

Part A - SAD in healthy subjects

EXPERIMENTAL

A randomized, double-blinded, placebo-controlled, single ascending dose (SAD) study in healthy male and/or female subjects. Subjects will receive DM199 subcutaneously (sc).

Drug: DM199

Part B - SAD in type 2 diabetic patients

EXPERIMENTAL

A randomized, partially double-blinded, placebo-controlled, sequential SAD study in male and/or female type 2 diabetes mellitus patients. Subjects will receive DM199 subcutaneously (sc).

Drug: DM199

Part C - MAD in healthy subjects

EXPERIMENTAL

A randomized, double-blinded, placebo-controlled, 14-day multiple ascending dose (MAD) study in healthy male and/or female subjects each. Subjects will receive sequential doses of DM199 sc for 14 days.

Drug: DM199

Part D - POC in type 2 diabetes patients

EXPERIMENTAL

A randomized, double-blinded, placebo-controlled, 28-day multiple-dose proof of concept (POC) study in male and/or female type 2 diabetes mellitus patients. Subjects will receive doses of DM199 sc for 28 days.

Drug: DM199

Part A - Healthy subjects SAD placebo

PLACEBO COMPARATOR

A randomized, double-blinded, placebo-controlled, single ascending dose (SAD) study in healthy male and/or female subjects. Subjects will receive placebo subcutaneously (sc).

Drug: Placebo

Part B - Type 2 diabetic patients SAD placebo

PLACEBO COMPARATOR

A randomized, partially double-blinded, placebo-controlled, sequential SAD study in male and/or female type 2 diabetes mellitus patients. Subjects will receive placebo subcutaneously (sc).

Drug: Placebo

Part C - Healthy subjects MAD placebo

PLACEBO COMPARATOR

A randomized, double-blinded, placebo-controlled, 14-day multiple ascending dose (MAD) study in healthy male and/or female subjects each. Subjects will receive placebo sc for 14 days.

Drug: Placebo

Part D - Type 2 diabetic patients POC placebo

PLACEBO COMPARATOR

A randomized, double-blinded, placebo-controlled, 28-day multiple-dose proof of concept (POC) study in male and/or female type 2 diabetes mellitus patients. Subjects will receive placebo sc for 28 days.

Drug: Placebo

Interventions

DM199 DRUG

Also known as: recombinant human tissue kallikrein-1, tissue kallikrein-1

Part A - SAD in healthy subjects; Part B - SAD in type 2 diabetic patients; Part C - MAD in healthy subjects; Part D - POC in type 2 diabetes patients

Placebo DRUG

Part A - Healthy subjects SAD placebo; Part B - Type 2 diabetic patients SAD placebo; Part C - Healthy subjects MAD placebo; Part D - Type 2 diabetic patients POC placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Status : Parts A and C: healthy subjects
• Parts B and D: type 2 diabetes mellitus patients :
• Body Mass Index : Parts A and C: 18.0 - 30.0 kg/m2
• Parts B and D: 25.0 - 35.0 kg/m2
• 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
• 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)
• 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
• Medical history without clinically significant abnormalities
• 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.
• 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
• 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

You may not qualify if:

• Evidence of clinically relevant pathology
• Pregnancy or lactation
• 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.
• 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)
• Positive drug screen (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants and alcohol)
• 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)
• Positive screen on HBsAg, anti-HCV or anti-HIV 1/2
• Illness within 7 days prior to (the first) drug administration
• Serum creatinine \> upper limit of the normal (ULN) range
• The use of insulin and thiazolidinediones for type 2 diabetes mellitus 3 months prior to screening is not allowed.
• The use of angiotensin converting enzyme (ACE) inhibitors 1 month prior to screening is not allowed.
• History of diabetic ketoacidosis or hyperosmolar coma
• Advanced diabetic complications, including neuropathy, nephropathy, retinopathy or other symptoms

Sponsors & Collaborators

• DiaMedica Therapeutics Inc: lead

Study Sites (1)

PRA

Zuidlaren, 9471 GP, Netherlands

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

DM199

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Salah Hadi, MD, MSc

  PRA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2013
• First Posted: May 3, 2013
• Study Start: April 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: November 1, 2014
• Last Updated: December 19, 2014

Record last verified: 2014-12

Locations

NL (1)