<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/NCT02206568</url>
  </required_header>
  <id_info>
    <org_study_id>PER511</org_study_id>
    <nct_id>NCT02206568</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Ultra-Rapid-Acting Insulin Lispro (URAL) in Type 1 Diabetes Mellitus</brief_title>
  <official_title>A Randomised Trial Investigating Pharmacokinetic Properties of Ultra-Rapid-Acting Insulin Lispro (URAL) in Subjects With Type 1 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Profil Institut für Stoffwechselforschung GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>AMAG Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To compare the early pharmacokinetic exposure of URAL and insulin lispro (ILisp).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To compare the total pharmacodynamic response of URAL and insulin lispro.&#xD;
&#xD;
      To compare the total pharmacokinetic exposure between URAL and insulin lispro.&#xD;
&#xD;
      To assess the safety and tolerability of URAL and insulin lispro.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">August 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics of URAL</measure>
    <time_frame>1 day</time_frame>
    <description>Area under the serum insulin lispro concentration-time curve from 0-30 minutes after administration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Onset of appearance of serum insulin lispro</measure>
    <time_frame>1 day</time_frame>
    <description>Measurement of time to reach insulin lispro concentration &gt;30 pmol/L in the serum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>1 day</time_frame>
    <description>Assessment of safety and tolerability of URAL</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Type 1 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>URAL vs. Insulin lispro</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will randomly be allocated to a treatment sequence consisting of 2 dosing visits during which the subject in a euglycaemic clamp setting will receive either a single dose of insulin lispro or URAL at predefined fixed dose levels in a randomized order.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>URAL</intervention_name>
    <arm_group_label>URAL vs. Insulin lispro</arm_group_label>
    <other_name>Ultra-Rapid-Acting Insulin Lispro</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent&#xD;
&#xD;
          2. Male subjects age 18-65 years inclusive&#xD;
&#xD;
          3. Type 1 diabetes mellitus diagnosed clinically &gt;= 12 months&#xD;
&#xD;
          4. Treatment with multiple daily insulin injections or CSII &gt;= 12 months&#xD;
&#xD;
          5. Current total daily insulin treatment &lt;1.2 (I)U/kg/day&#xD;
&#xD;
          6. Current total daily bolus insulin treatment &lt;0.7 (I)U/kg/day&#xD;
&#xD;
          7. Body mass index 18.0-30.0 kg/m2 inclusive&#xD;
&#xD;
          8. HbA1c =&lt;9.0% by local laboratory analysis (one retest within a week is permitted with&#xD;
             the result of the last test being conclusive)&#xD;
&#xD;
          9. C-peptide =&lt; 0.30 nmol/L&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known or suspected hypersensitivity to trial products or related products&#xD;
&#xD;
          2. Previous participation in this trial. .&#xD;
&#xD;
          3. Receipt of any non-marketed investigational product within 3 months&#xD;
&#xD;
          4. Clinically significant abnormal haematology, biochemistry, liver enzymes, or&#xD;
             coagulation screening tests&#xD;
&#xD;
          5. Suffer from or history of a life threatening disease or any clinically significant&#xD;
             cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal,&#xD;
             endocrinological, haematological, dermatological, venereal , neurological, psychiatric&#xD;
             diseases or other major disorders&#xD;
&#xD;
          6. History of deep leg vein thrombosis or a frequent appearance of deep leg vein&#xD;
             thrombosis in 1st degree relatives&#xD;
&#xD;
          7. Cardiac problems defined as decompensated heart failure (New York Heart Association&#xD;
             class III and IV) at any time and/or angina pectoris within the last 12 months and/or&#xD;
             acute myocardial infarction at any time.&#xD;
&#xD;
          8. Supine blood pressure at screening outside the range of 90-140 mmHg for systolic or&#xD;
             50-90 mmHg for diastolic . Pulse outside 50 to 90 bpm.&#xD;
&#xD;
          9. Clinically significant abnormal ECG at screening.&#xD;
&#xD;
         10. Proliferative retinopathy or maculopathy and/or severe neuropathy, in particular&#xD;
             autonomic neuropathy.&#xD;
&#xD;
         11. Any disease or condition that, in the opinion of the Investigator, would represent an&#xD;
             unacceptable risk for the subject's safety.&#xD;
&#xD;
         12. Subject positive for HBs-Ag, HCV-Ab&#xD;
&#xD;
         13. Positive result to the screening test for HIV-1 antibodies, HIV-2 antibodies, or HIV-1&#xD;
             antigen according to locally used diagnostic testing.&#xD;
&#xD;
         14. History of multiple and/or severe allergies to drugs or foods or a history of severe&#xD;
             anaphylactic reaction.&#xD;
&#xD;
         15. Subject who has donated blood or plasma in the past month or more than 500 mL within 3&#xD;
             months.&#xD;
&#xD;
         16. Surgery or trauma with significant blood loss (more than 500 mL) within 3 months.&#xD;
&#xD;
         17. Current treatment with systemic (oral, IV, or inhaled) corticosteroids, monoamine&#xD;
             oxidase inhibitors, NSAID, prostaglandin blockers, systemic non-selective&#xD;
             beta-blockers, growth hormone (last 3 months), non-routine vitamins or herbal products&#xD;
             (last 2 weeks). Thyroid hormones are not allowed unless the use of these has been&#xD;
             stable during the last 3 months. Routine vitamins are permitted up to 48 hours prior&#xD;
             to dosing.&#xD;
&#xD;
         18. Significant history of alcoholism and/or drug/chemical abuse as per Investigator's&#xD;
             judgement or a positive result in the urine drug/alcohol breath test screen at the&#xD;
             screening visit.&#xD;
&#xD;
         19. Heavy smoker&#xD;
&#xD;
         20. Not able or willing to refrain from smoking and use of nicotine.&#xD;
&#xD;
         21. Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemia event during the last&#xD;
             12 months) or hypoglycaemic unawareness.&#xD;
&#xD;
         22. Subject with mental incapacity or language barriers precluding adequate understanding.&#xD;
&#xD;
         23. Potentially non-compliant or uncooperative during the trial.&#xD;
&#xD;
         24. Any condition that would interfere with trial participation or evaluation of results.&#xD;
&#xD;
         25. No relevant lipodystrophy within the area of drug administration and Doppler&#xD;
             sonography.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alin Stirban, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Profil Institut fur Stoffwechselforschung GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Profil Institut fur Stoffwechselforschung GmbH</name>
      <address>
        <city>Neuss</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>May 2015</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>July 14, 2020</last_update_submitted>
  <last_update_submitted_qc>July 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 15, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>diabetes mellitus</keyword>
  <keyword>phase 1</keyword>
  <keyword>insulin lispro</keyword>
  <keyword>male subjects</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 1</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Lispro</mesh_term>
    <mesh_term>Insulin, Short-Acting</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02206568
org study id: PER511
nct id: NCT02206568
lead sponsor: 
collaborator: 
has dmc: Yes
To compare the early pharmacokinetic exposure of URAL and insulin lispro (ILisp).
To compare the total pharmacodynamic response of URAL and insulin lispro.

      To compare the total pharmacokinetic exposure between URAL and insulin lispro.

      To assess the safety and tolerability of URAL and insulin lispro.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: Triple (Participant, Care Provider, Investigator)
measure: Pharmacokinetics of URAL
time frame: 1 day
description: Area under the serum insulin lispro concentration-time curve from 0-30 minutes after administration
measure: Onset of appearance of serum insulin lispro
time frame: 1 day
description: Measurement of time to reach insulin lispro concentration >30 pmol/L in the serum
measure: Number of subjects with adverse events
time frame: 1 day
description: Assessment of safety and tolerability of URAL
arm group label: URAL vs. Insulin lispro
arm group type: Experimental
description: Each subject will randomly be allocated to a treatment sequence consisting of 2 dosing visits during which the subject in a euglycaemic clamp setting will receive either a single dose of insulin lispro or URAL at predefined fixed dose levels in a randomized order.
intervention type: Drug
intervention name: URAL
arm group label: URAL vs. Insulin lispro
other name: Ultra-Rapid-Acting Insulin Lispro
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Alin Stirban, MD
role: Principal Investigator
affiliation: Profil Institut fur Stoffwechselforschung GmbH
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Insulin Lispro
mesh term: Insulin, Short-Acting