<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03795389</url>
  </required_header>
  <id_info>
    <org_study_id>DM199-2018-001</org_study_id>
    <nct_id>NCT03795389</nct_id>
  </id_info>
  <brief_title>Study to Assess PK, Safety and Tolerability in Patients With DM and CKD</brief_title>
  <official_title>A Multi-Center Open-label Investigation to Assess the Pharmacokinetics, Safety and Tolerability of DM199 in Patients With Diabetes Mellitus and Chronic Kidney Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>DiaMedica Therapeutics Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>DiaMedica Therapeutics Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      An open-label, phase IB, multi-center study evaluating DM199 in subjects with Type 1 Diabetes&#xD;
      or Type 2 Diabetes and Stage 3 or 4 Chronic Kidney Disease. The primary objectives of this&#xD;
      study are to evaluate safety, tolerability, and PK profile of DM199 in these subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study evaluates the safety, tolerability, and PK profile of DM199 in subjects with T1D or&#xD;
      T2D and with Stage 3 or Stage 4 CKD. Additionally, this study evaluates urine concentrations&#xD;
      of KLK1 pre and post dose.&#xD;
&#xD;
      Cohort 1: Subjects with T1D or T2D and Stage 3 CKD will be administered one of three DM199&#xD;
      doses: 3.0 ug/kg or 5.0 ug/kg or 8.0 ug/kg single SC dose. Cohort 2: Subjects with T1D or T2D&#xD;
      and Stage 4 CKD will be administered a single 3.0 µg/kg single SC dose. Secondary and&#xD;
      exploratory study objectives include collection and analysis of vital signs, biomarkers,&#xD;
      eGFR, blood glucose, and ECG's.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 12, 2019</start_date>
  <completion_date type="Actual">July 21, 2019</completion_date>
  <primary_completion_date type="Actual">July 21, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety as assessed by incidence, severity, and causality of adverse events</measure>
    <time_frame>11 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Tolerability as assessed by incidence and severity of AEs</measure>
    <time_frame>11 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>plasma measurements of DM199</measure>
    <time_frame>11 days</time_frame>
    <description>as measured in the three different dosing groups; 3.0 ug/kg, 5.0 ug/kg, and 8.0 ug/kg.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DM199 urine concentrations of KLK1</measure>
    <time_frame>11 days</time_frame>
    <description>urine KLK1 will be measured pre and post study drug administration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>C Reactive protein (CRP)</measure>
    <time_frame>11 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Matrix Metalloproteinase-9 (MMP-9)</measure>
    <time_frame>11 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular Endothelial Growth Factor (VEGF)</measure>
    <time_frame>11 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nitric Oxide (NO)</measure>
    <time_frame>11 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum creatinine</measure>
    <time_frame>11 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cystatin C</measure>
    <time_frame>11 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>neutrophil gelatinase-associated prostaglandin E2</measure>
    <time_frame>11 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine Kidney Injury Molecule-1 (Kim1)</measure>
    <time_frame>11 days</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>serum creatinine</measure>
    <time_frame>11 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Blood glucose</measure>
    <time_frame>11 days</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Chronic Kidney Disease</condition>
  <condition>Chronic Kidney Disease, Stage 3 (Moderate)</condition>
  <condition>Chronic Kidney Disease, Stage 4 (Severe)</condition>
  <condition>Diabetes</condition>
  <arm_group>
    <arm_group_label>3.0 µg/kg SC, single dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>n=8, study group of T1D or T2D with stage 3 CKD. separate n=8 of study group with T1D or T2D with CKD stage 4).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>5.0 µg/kg SC, single dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>n=8, study group of T1D or T2D with stage 3 CKD.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>8.0 µg/kg SC, single dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>n=8, study group of T1D or T2D with stage 3 CKD.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DM199</intervention_name>
    <description>Single SC dose</description>
    <arm_group_label>3.0 µg/kg SC, single dose</arm_group_label>
    <arm_group_label>5.0 µg/kg SC, single dose</arm_group_label>
    <arm_group_label>8.0 µg/kg SC, single dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject is willing and able to provide informed consent for study participation.&#xD;
&#xD;
          -  Subject is ≥ 18 years of age.&#xD;
&#xD;
          -  Subject has an established diagnosis of T1D or T2D as determined by medical evaluation&#xD;
             at screen.&#xD;
&#xD;
          -  Subjects A1c &lt;9.8%&#xD;
&#xD;
          -  Subject is clinically stable with respect to underlying renal impairment and diabetes,&#xD;
             as assessed by the Investigator's medical evaluation.&#xD;
&#xD;
          -  Subject has been diagnosed with Stage 3 CKD as defined by eGFR (MDRD) between 30 - &lt;60&#xD;
             or Stage 4 as defined by eGFR &lt;30 (not on dialysis) at screening.&#xD;
&#xD;
          -  Subject has a body mass index (BMI) between 18 to 45 kg/m2 (inclusive).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has positive drug test for drugs of abuse and/or positive alcohol breath test&#xD;
             at screening and Day 0.&#xD;
&#xD;
          -  Subject is unable or unwilling to comply with protocol requirements, including&#xD;
             assessments, tests, and follow-up visits.&#xD;
&#xD;
          -  Subject has a history of significant allergic diathesis such as urticaria, angioedema,&#xD;
             or anaphylaxis.&#xD;
&#xD;
          -  Subject has had any live vaccination ≤ 3 months prior to enrollment or will require&#xD;
             vaccination during the study.&#xD;
&#xD;
          -  Subject must not be taking an ACEi medication for 5 half-lives prior to study drug&#xD;
             administration and for 5 days post study drug administration.&#xD;
&#xD;
          -  Subject is unwilling or unable to limit smoking to ≤ 10 cigarettes per day (or other&#xD;
             products that contain nicotine limited to &lt; 200 mg of nicotine/day) during the study&#xD;
             participation period.&#xD;
&#xD;
          -  Subject has a current malignancy or active malignancy ≤ 3 years prior to enrollment&#xD;
             except basal cell or squamous cell carcinoma of the skin or in situ cervical cancer&#xD;
             that has undergone potentially curative therapy and ≥ six months have elapsed since&#xD;
             the procedure.&#xD;
&#xD;
          -  Subject has an active infection at the time of enrollment, and/or a history of&#xD;
             clinically significant acute bacterial, viral, or fungal systemic infections that&#xD;
             required systemic treatment in the last four weeks prior to enrollment.&#xD;
&#xD;
          -  Subject has known medical history of alpha 1-antitrypsin deficiency (α1-antitrypsin&#xD;
             deficiency).&#xD;
&#xD;
          -  Subject has serological evidence of human immunodeficiency virus (HIV), hepatitis B&#xD;
             surface antigen (HBsAg), or anti-hepatitis C virus (Anti-HCV) at screen.&#xD;
&#xD;
          -  Subject is pregnant or nursing or is planning a pregnancy during the study period.&#xD;
&#xD;
          -  Subject is male or female of childbearing potential, is participating in sexual&#xD;
             activity that could lead to pregnancy and is unable or unwilling to practice medically&#xD;
             effective contraception during the study.&#xD;
&#xD;
          -  Subject has received any investigational drug or device within 14 days (or 5 half&#xD;
             lives, whichever is longer) prior to study drug administration on Day 1&#xD;
&#xD;
          -  Subject has renal artery stenosis as determine at screen with medical history.&#xD;
&#xD;
          -  Subject has hypotension as defined by systolic blood pressure ≤ 90 and diastolic blood&#xD;
             pressure ≤ 60 mmHg.&#xD;
&#xD;
          -  Subject has Proteinuria: PCR&gt;2000mg/gm (spot testing).&#xD;
&#xD;
          -  Subject does not have adequate venous access for blood sampling.&#xD;
&#xD;
          -  Subject has any other medical condition which, in the opinion of the Investigator,&#xD;
             will make participation medically unsafe or interfere with the study results.&#xD;
&#xD;
          -  Subject has any other clinically significant abnormalities in laboratory test results&#xD;
             at screening that would, in the opinion of the Investigator, increase the subject's&#xD;
             risk of participation, jeopardize complete participation in the study, or compromise&#xD;
             interpretation of study data.&#xD;
&#xD;
          -  Subject has any of the following conditions as determined by ECG or medical record:&#xD;
&#xD;
               -  Any significant arrhythmia or conduction abnormality, which, in the opinion of&#xD;
                  the Investigators and Medical Monitor, may interfere with the safety of the&#xD;
                  subject.&#xD;
&#xD;
          -  Subject is taking Cimetidine, St. John's Wort, or any other herbal or probiotic&#xD;
             supplement.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Harry Alcorn, Pharm.D.</last_name>
    <role>Study Director</role>
    <affiliation>DiaMedica Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Pharmacology of Miami</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orlando Clinical Research Center Inc</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prism Research</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>January 3, 2019</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>September 3, 2021</last_update_submitted>
  <last_update_submitted_qc>September 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetes</keyword>
  <keyword>Chronic Kidney Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03795389
org study id: DM199-2018-001
nct id: NCT03795389
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
An open-label, phase IB, multi-center study evaluating DM199 in subjects with Type 1 Diabetes
      or Type 2 Diabetes and Stage 3 or 4 Chronic Kidney Disease. The primary objectives of this
      study are to evaluate safety, tolerability, and PK profile of DM199 in these subjects.
The study evaluates the safety, tolerability, and PK profile of DM199 in subjects with T1D or
      T2D and with Stage 3 or Stage 4 CKD. Additionally, this study evaluates urine concentrations
      of KLK1 pre and post dose.

      Cohort 1: Subjects with T1D or T2D and Stage 3 CKD will be administered one of three DM199
      doses: 3.0 ug/kg or 5.0 ug/kg or 8.0 ug/kg single SC dose. Cohort 2: Subjects with T1D or T2D
      and Stage 4 CKD will be administered a single 3.0 µg/kg single SC dose. Secondary and
      exploratory study objectives include collection and analysis of vital signs, biomarkers,
      eGFR, blood glucose, and ECG's.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety as assessed by incidence, severity, and causality of adverse events
time frame: 11 days
measure: Tolerability as assessed by incidence and severity of AEs
time frame: 11 days
measure: plasma measurements of DM199
time frame: 11 days
description: as measured in the three different dosing groups; 3.0 ug/kg, 5.0 ug/kg, and 8.0 ug/kg.
measure: DM199 urine concentrations of KLK1
time frame: 11 days
description: urine KLK1 will be measured pre and post study drug administration.
measure: C Reactive protein (CRP)
time frame: 11 days
measure: Matrix Metalloproteinase-9 (MMP-9)
time frame: 11 days
measure: Vascular Endothelial Growth Factor (VEGF)
time frame: 11 days
measure: Nitric Oxide (NO)
time frame: 11 days
measure: Serum creatinine
time frame: 11 days
measure: Cystatin C
time frame: 11 days
measure: neutrophil gelatinase-associated prostaglandin E2
time frame: 11 days
measure: Urine Kidney Injury Molecule-1 (Kim1)
time frame: 11 days
measure: serum creatinine
time frame: 11 days
measure: Blood glucose
time frame: 11 days
arm group label: 3.0 µg/kg SC, single dose
arm group type: Experimental
description: n=8, study group of T1D or T2D with stage 3 CKD. separate n=8 of study group with T1D or T2D with CKD stage 4).
arm group label: 5.0 µg/kg SC, single dose
arm group type: Experimental
description: n=8, study group of T1D or T2D with stage 3 CKD.
arm group label: 8.0 µg/kg SC, single dose
arm group type: Experimental
description: n=8, study group of T1D or T2D with stage 3 CKD.
intervention type: Drug
intervention name: DM199
description: Single SC dose
arm group label: 3.0 µg/kg SC, single dose
arm group label: 5.0 µg/kg SC, single dose
arm group label: 8.0 µg/kg SC, single dose
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Harry Alcorn, Pharm.D.
role: Study Director
affiliation: DiaMedica Inc.
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
sharing ipd: No