<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/NCT03278158</url>
  </required_header>
  <id_info>
    <org_study_id>PP-CT01</org_study_id>
    <nct_id>NCT03278158</nct_id>
  </id_info>
  <brief_title>A Single-dose Trial to Investigate the Safety and Tolerability of XEN-D0501 in Patients With Diabetes Mellitus Type 2</brief_title>
  <official_title>A Single-dose Dose Escalation Trial in a Randomised, Single-blind, Placebo-controlled Group-comparison Design to Investigate the Safety and Tolerability of XEN-D0501 in Patients With Diabetes Mellitus Type 2</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pila Pharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pila Pharma</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-dose dose escalation trial in a randomised, single-blind, placebo-controlled&#xD;
      group-comparison design to investigate the safety and tolerability of XEN-D0501 in subjects&#xD;
      with diabetes mellitus type 2 where life style changes and treatment with metformin has&#xD;
      failed to effectively reduce blood glucose concentrations.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 18, 2017</start_date>
  <completion_date type="Actual">November 13, 2018</completion_date>
  <primary_completion_date type="Actual">November 13, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Each subject will be randomised to one of four treatments, placebo and three different single oral doses of XEN-D0501. Cohorts of 8 patients are run subsequently where of 2 patients receive placebo and 6 patients receive XEN-D0501 beginning with the 1 mg dose followed by the 2, 4 and 8 mg dose groups. Each treatment step will be completed consecutively and progression to next dose level depend on good safety and tolerability on the previous dose level.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>The type of treatment is blinded for the subjects.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability of single ascending oral doses of XEN-D0501, (1, 2, 4 and 8 mg) versus placebo in type 2 diabetic patients in treatment with metformin (Incidence of adverse events in type 2 diabetic patients)</measure>
    <time_frame>1-3 weeks</time_frame>
    <description>Incidence of adverse events in type 2 diabetic patients</description>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects in the placebo arm will receive a single oral tablet containing no active drug.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>XEN-D0501, 1 mg/tablet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm will receive a single oral tablet of XEN-D0501, 1 mg/tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>XEN-D0501, 2 mg/tablet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm will receive a single oral tablet of XEN-D0501, 2 mg/tablet. Discontinued after 2 patients due to good safety. Escalation to higher dose levels in whole study (1, 2 and 4 mg changed to 1, 4 and 8 mg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>XEN-D0501, 4 mg/tablet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm will receive a single oral tablet of XEN-D0501, 4 mg/tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>XEN-D0501, 8 mg/tablet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm will receive a single oral tablet of XEN-D0501, 8 mg/tablet</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects in the placebo arm will receive a single oral tablet containing no active drug.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>XEN-D0501, 1 mg/tablet</intervention_name>
    <description>Subjects in this arm will receive a single oral tablet of XEN-D0501, 1 mg/tablet</description>
    <arm_group_label>XEN-D0501, 1 mg/tablet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>XEN-D0501, 2 mg/tablet</intervention_name>
    <description>Subjects in this arm will receive a single oral tablet of XEN-D0501, 2 mg/tablet</description>
    <arm_group_label>XEN-D0501, 2 mg/tablet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>XEN-D0501, 4 mg/tablet</intervention_name>
    <description>Subjects in this arm will receive a single oral tablet of XEN-D0501, 4 mg/tablet</description>
    <arm_group_label>XEN-D0501, 4 mg/tablet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>XEN-D0501, 8 mg/tablet</intervention_name>
    <description>Subjects in this arm will receive a single oral tablet of XEN-D0501, 8 mg/tablet</description>
    <arm_group_label>XEN-D0501, 8 mg/tablet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The subject must give his/her signed and dated informed consent before any&#xD;
             trial-related activities. Trial-related activities are any procedures that would not&#xD;
             have been performed during the normal management of the subject.&#xD;
&#xD;
          2. Diagnosis of type 2 diabetes mellitus&#xD;
&#xD;
          3. In treatment with metformin, but no other anti-diabetic drugs&#xD;
&#xD;
          4. In treatment with an ACE-inhibitor but no other anti-hypertensive drugs&#xD;
&#xD;
          5. HbA1C (glycosylated haemoglobin A1C) 6.5-10 %&#xD;
&#xD;
          6. Age between 30 and 70 years (both inclusive).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. A subject with a history of significant multiple drug allergies or with a known or&#xD;
             suspected allergy to the trial product or any medicine chemically related to the trial&#xD;
             product, as judged by the Investigator.&#xD;
&#xD;
          2. A subject who has a supine blood pressure at screening (including those on&#xD;
             anti-hypertensives), after resting for 5 min, outside the range of 90-140 mmHg&#xD;
             systolic or 50-90 mmHg diastolic (excluding white-coat hypertension; therefore, if a&#xD;
             repeated measurement on a second screening visit shows values within the range, the&#xD;
             subject can be included in the trial).&#xD;
&#xD;
          3. A subject who is in pharmacological treatment of hypertension if the current treatment&#xD;
             includes other than an ACE-inhibitor&#xD;
&#xD;
          4. A subject who has a clinically significant abnormal ECG at screening, as judged by the&#xD;
             investigator.&#xD;
&#xD;
          5. A subject who has participated in any other trials involving investigational products&#xD;
             within the 3 months preceding the start of dosing.&#xD;
&#xD;
          6. A subject who has donated any blood or plasma in the past month or in excess of 500 mL&#xD;
             within the 3 months preceding screening.&#xD;
&#xD;
          7. A subject who has a significant history of alcoholism or drug/chemical abuse as per&#xD;
             investigator's judgement, or who has a positive result in the urine drug/alcohol&#xD;
             screen at screening visit.&#xD;
&#xD;
          8. A subject who smokes more than 5 cigarettes, or the equivalent, per day and is unable&#xD;
             to refrain from smoking during the in-house periods as determined by the Investigator.&#xD;
&#xD;
          9. A subject with mental incapacity or language barriers which preclude adequate&#xD;
             understanding or cooperation, who is unwilling to participate in the trial, or who in&#xD;
             the opinion of their general practitioner or the Investigator should not participate&#xD;
             in the trial.&#xD;
&#xD;
         10. Surgery or trauma with significant blood loss within the last 2 months prior to&#xD;
             dosing.&#xD;
&#xD;
         11. A subject with a history of or presence of cancer, or any clinically significant,&#xD;
             respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological (with the&#xD;
             exception of diabetes mellitus type 2 and euthyroid struma), haematological,&#xD;
             dermatological, venereal, neurological, psychiatric diseases or other major disorders.&#xD;
&#xD;
         12. Cardiac problems defined as: decompensated heart failure (New York Heart Association&#xD;
             (NYHA) class III and IV) at any time and/or angina pectoris and/or acute myocardial&#xD;
             infarction within the last 12 months.&#xD;
&#xD;
         13. A subject with a clinically significant abnormal haematology or biochemistry tests at&#xD;
             screening visit, as judged by the Investigator considering the underlying disease.&#xD;
&#xD;
         14. Current treatment with drugs known to interfere with glucose metabolism such as&#xD;
             systemic corticoids and monoamine oxidase inhibitors (MAO) inhibitors.&#xD;
&#xD;
         15. A subject who has proliferative retinopathy or maculopathy, and/or severe neuropathy,&#xD;
             in particular autonomic neuropathy, as judged by the Investigator.&#xD;
&#xD;
         16. Haemoglobin &lt; 6.2 mmol/l, total leukocyte count &lt; 3.0 x 109/l, thrombocytes &lt;100 x&#xD;
             109/l, serum creatinine levels ≥ 126 µmol/l (male) or ≥ 111 µmol/l (female), bilirubin&#xD;
             &gt; 3 x ULN, alanine aminotransferase &gt; 2 x the upper limit of normal (ULN), alkaline&#xD;
             phosphatase &gt; 2 x ULN, one re-test within a week is permitted.&#xD;
&#xD;
         17. Previous participation (randomisation) in this trial.&#xD;
&#xD;
         18. Any condition that would interfere with trial participation or evaluation of results,&#xD;
             as judged by the investigator and/or sponsor&#xD;
&#xD;
         19. Recurrent major hypoglycaemia or hypoglycaemic unawareness, as judged by the&#xD;
             Investigator.&#xD;
&#xD;
         20. Females of childbearing potential who are pregnant, breast-feeding or intend to become&#xD;
             pregnant or are not using adequate contraceptive methods (Adequate contraceptive&#xD;
             measures include sterilisation, hormonal intrauterine devices, oral hormonal&#xD;
             contraceptives (p-pills), implantants, transdermal patches, p-ring or depot injection,&#xD;
             sexual abstinence or vasectomised partner). A male subject who is sexually active and&#xD;
             has not been surgically sterilised must be informed that he must ensure that his&#xD;
             partner practices effective contraception, as stated above, or he must refrain from&#xD;
             sexual intercourse during the trial and until 90 days after completion of the trial.&#xD;
             This is to prevent the possibility of a pregnancy from spermatocytes that can&#xD;
             potentially be damaged by trial medication.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Henning Beck-Nielsen, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Odense University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Odense University Hospital</name>
      <address>
        <city>Odense</city>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <last_update_submitted>March 19, 2019</last_update_submitted>
  <last_update_submitted_qc>March 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>safety</keyword>
  <keyword>tolerability</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</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/NCT03278158
org study id: PP-CT01
nct id: NCT03278158
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a single-dose dose escalation trial in a randomised, single-blind, placebo-controlled
      group-comparison design to investigate the safety and tolerability of XEN-D0501 in subjects
      with diabetes mellitus type 2 where life style changes and treatment with metformin has
      failed to effectively reduce blood glucose concentrations.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Each subject will be randomised to one of four treatments, placebo and three different single oral doses of XEN-D0501. Cohorts of 8 patients are run subsequently where of 2 patients receive placebo and 6 patients receive XEN-D0501 beginning with the 1 mg dose followed by the 2, 4 and 8 mg dose groups. Each treatment step will be completed consecutively and progression to next dose level depend on good safety and tolerability on the previous dose level.
primary purpose: Treatment
masking: Single (Participant)
masking description: The type of treatment is blinded for the subjects.
measure: Safety and tolerability of single ascending oral doses of XEN-D0501, (1, 2, 4 and 8 mg) versus placebo in type 2 diabetic patients in treatment with metformin (Incidence of adverse events in type 2 diabetic patients)
time frame: 1-3 weeks
description: Incidence of adverse events in type 2 diabetic patients
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects in the placebo arm will receive a single oral tablet containing no active drug.
arm group label: XEN-D0501, 1 mg/tablet
arm group type: Experimental
description: Subjects in this arm will receive a single oral tablet of XEN-D0501, 1 mg/tablet
arm group label: XEN-D0501, 2 mg/tablet
arm group type: Experimental
description: Subjects in this arm will receive a single oral tablet of XEN-D0501, 2 mg/tablet. Discontinued after 2 patients due to good safety. Escalation to higher dose levels in whole study (1, 2 and 4 mg changed to 1, 4 and 8 mg)
arm group label: XEN-D0501, 4 mg/tablet
arm group type: Experimental
description: Subjects in this arm will receive a single oral tablet of XEN-D0501, 4 mg/tablet
arm group label: XEN-D0501, 8 mg/tablet
arm group type: Experimental
description: Subjects in this arm will receive a single oral tablet of XEN-D0501, 8 mg/tablet
intervention type: Drug
intervention name: Placebo
description: Subjects in the placebo arm will receive a single oral tablet containing no active drug.
arm group label: Placebo
intervention type: Drug
intervention name: XEN-D0501, 1 mg/tablet
description: Subjects in this arm will receive a single oral tablet of XEN-D0501, 1 mg/tablet
arm group label: XEN-D0501, 1 mg/tablet
intervention type: Drug
intervention name: XEN-D0501, 2 mg/tablet
description: Subjects in this arm will receive a single oral tablet of XEN-D0501, 2 mg/tablet
arm group label: XEN-D0501, 2 mg/tablet
intervention type: Drug
intervention name: XEN-D0501, 4 mg/tablet
description: Subjects in this arm will receive a single oral tablet of XEN-D0501, 4 mg/tablet
arm group label: XEN-D0501, 4 mg/tablet
intervention type: Drug
intervention name: XEN-D0501, 8 mg/tablet
description: Subjects in this arm will receive a single oral tablet of XEN-D0501, 8 mg/tablet
arm group label: XEN-D0501, 8 mg/tablet
criteria: 
gender: All
minimum age: 30 Years
maximum age: 70 Years
healthy volunteers: No
last name: Henning Beck-Nielsen, Dr.
role: Principal Investigator
affiliation: Odense University Hospital
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
sharing ipd: No