A Study to Evaluate the Safety and Effectiveness of DM199 in Healthy Subjects and Type 2 Diabetes Patients
Condition: Diabetes Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1/Phase 2

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).
    

Detailed description: 
      DM199 (recombinant human tissue kallikrein-1) is being developed as a new biological
      treatment for type 2 diabetes mellitus. This is a first-in-human study for DM199 and is a
      4-part, single center study in healthy subjects and type 2 diabetes mellitus patients.

      Part A will be a randomized, double-blinded, placebo-controlled, single ascending dose (SAD)
      study in healthy male and/or female subjects. Subjects will receive DM199 or placebo
      subcutaneously (sc).

      Part B will be a randomized, partially double-blinded, placebo-controlled, sequential SAD
      study in male and/or female type 2 diabetes mellitus patients.

      Part C will be 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 DM-199 or placebo sc for 14 days.

      Part D will be 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 parallel doses of DM199 or placebo sc for 28 days.

      The primary objective is to evaluate the safety and tolerability of single and multiple
      subcutaneous doses of DM199 in healthy subjects and type 2 diabetes mellitus patients.
      Another objective is to 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.

      Secondary objectives include determining the effect of DM199 on glucose homeostasis (via
      fasting glucose and HbA1c levels), standardized meal tolerance test, C-peptide, fructosamine,
      GLP-1 (active and total), glucagon, adiponectin and lipids measurements, and homeostatic
      model assessment of insulin resistance/beta cell function (HOMA) determination in type 2
      diabetes mellitus patients; assessing the formation of antibodies to DM199 after
      administration of multiple doses of DM199 in healthy subjects and type 2 diabetes mellitus
      patients; and determining changes in immune cell populations by fluorescence-activated cell
      sorting analysis following multiple doses of DM199 in healthy subjects and type 2 diabetes
      mellitus patients
    

Intervention name(s): DM199; Placebo
Intervention type(s): Drug; Drug
Other intervention name(s): recombinant human tissue kallikrein-1; tissue kallikrein-1
Intervention MeSH terms: Kallikreins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
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