<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/NCT01724814</url>
  </required_header>
  <id_info>
    <org_study_id>HM-INS-101</org_study_id>
    <nct_id>NCT01724814</nct_id>
  </id_info>
  <brief_title>A First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM12460A</brief_title>
  <acronym>HM12460A</acronym>
  <official_title>A First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM12460A</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hanmi Pharmaceutical Company Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hanmi Pharmaceutical Company Limited</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study Design:&#xD;
&#xD;
      Part 1.Randomized, double-blind, placebo-controlled, escalating single-dose design with&#xD;
      Healthy volunteers Part 2.Open , sequential, two-period, single dose study with type 1&#xD;
      diabetes Part 3.Open, sequential, two-period, single dose study with type 2 diabetes&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The principle objectives of this study are to assess safety and tolerability and to explore&#xD;
      pharmacokinetic(PK) and pharmacodynamic(PD) parameters of a single dose of a novel very-long&#xD;
      acting insulin formulation (HM12460A) in comparison to a single dose of human Neutral&#xD;
      Protamine Hagedorn (NPH) in healthy volunteers (part 1), subjects with type 1 diabetes (part&#xD;
      2) and in subjects with type 2 diabetes (part 3).&#xD;
&#xD;
      The study will incorporate adaptive elements to provide both PK and PD data. The dose of&#xD;
      HM12460A to be administered to the subjects with type 1 diabetes and type 2 diabetes will be&#xD;
      guided by PK data from part 1 of the study; the PD assessment of HM12460A in subjects with&#xD;
      diabetes will also be informed by knowledge of PK gained from the healthy volunteer study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 20, 2012</start_date>
  <completion_date type="Actual">July 1, 2014</completion_date>
  <primary_completion_date type="Actual">July 1, 2014</primary_completion_date>
  <phase>Phase 1</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence and severity of treatment emergent adverse events</measure>
    <time_frame>one year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration(Cmax) of HM12460A following a single dose in Parts 1-3</measure>
    <time_frame>one year</time_frame>
    <description>PK properties of HM12460A following a single dose in Parts 1-3 will be assessed in plasma using a validated assay</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">86</enrollment>
  <condition>Healthy</condition>
  <condition>Type 1 Diabetes Mellitus</condition>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Cohort S1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HM12460A Dose 1 (1.2 nmol/kg) or placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort S2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HM12460A Dose 2 (2.4 nmol/kg) or Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort S3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HM12460A Dose 3 (4.8 nmol/kg) or Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort S4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HM12460A Dose 4 (9.6 nmol/kg) or Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort S5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HM12460A Dose 5 (14.4 nmol/kg) or Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort S6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HM12460A Dose 6 (19.2 nmol/kg) or Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HM12460A</intervention_name>
    <description>Single dose SC administration ranging from 1.2 nmol/kg to 19.2 nmol/kg of HM12460A</description>
    <arm_group_label>Cohort S1</arm_group_label>
    <arm_group_label>Cohort S2</arm_group_label>
    <arm_group_label>Cohort S3</arm_group_label>
    <arm_group_label>Cohort S4</arm_group_label>
    <arm_group_label>Cohort S5</arm_group_label>
    <arm_group_label>Cohort S6</arm_group_label>
    <other_name>LAPS-Insulin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Singe dose SC administration of Placebo</description>
    <arm_group_label>Cohort S1</arm_group_label>
    <arm_group_label>Cohort S2</arm_group_label>
    <arm_group_label>Cohort S3</arm_group_label>
    <arm_group_label>Cohort S4</arm_group_label>
    <arm_group_label>Cohort S5</arm_group_label>
    <arm_group_label>Cohort S6</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Healthy subjects&#xD;
&#xD;
          -  Age ≥18 and ≤70 years&#xD;
&#xD;
          -  Non-obese; body mass index between 18.0 and 30.0 kg/m2 inclusive.&#xD;
&#xD;
          -  Considered generally healthy upon completion of medical history, physical examination&#xD;
             and biochemical investigations as judged by the Investigator.&#xD;
&#xD;
          -  Non-smoker, or light smoker, defined as &lt;15 cigarettes/day and able to abstain from&#xD;
             smoking during confinement period.&#xD;
&#xD;
          -  Females must be non-pregnant and non-lactating, and either surgically sterile (e.g.,&#xD;
             tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or&#xD;
             post-menopausal for &gt;12 months. Males must be surgically sterile, abstinent or if&#xD;
             engaged in sexual relations of child-bearing potential, the subject must be using an&#xD;
             acceptable contraceptive method during and for during a period of 60 days after the&#xD;
             last dose of Study Drug.&#xD;
&#xD;
          -  Signed and dated informed consent obtained before any trial-related activities.&#xD;
             (Trial-related activities are any procedure that would not have been performed during&#xD;
             normal management of the subject).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous participation in this trial or other clinical trials within the last 3&#xD;
             months.&#xD;
&#xD;
          -  Clinically significant abnormal hematology or biochemistry screening tests, as judged&#xD;
             by the Investigator. In particular, healthy subjects with liver enzymes above the&#xD;
             upper limit of the normal range and subjects with diabetes who have elevated liver&#xD;
             enzymes (AST or ALT &gt;2 times the upper limit of normal) or impaired renal function&#xD;
             (elevated serum creatinine values above the upper limit of normal) will be excluded.&#xD;
&#xD;
          -  History of any illness that, in the opinion of the Investigator, might confound the&#xD;
             results of the trial or pose risk in administering the trial drug to the subject. In&#xD;
             particular, subjects with significant cardiovascular disease, anemia (hemoglobin below&#xD;
             the lower limit of normal) or hemoglobinopathy will not be allowed to enter the trial.&#xD;
&#xD;
          -  Clinically significant abnormal ECG at screening, as judged by the Investigator.&#xD;
&#xD;
          -  History of alcohol abuse.&#xD;
&#xD;
          -  Any positive reaction of drugs of abuse.&#xD;
&#xD;
          -  Hepatitis B or C or HIV positive.&#xD;
&#xD;
          -  Use of prescription drugs within 3 weeks preceding the first dosing of insulin, except&#xD;
             for medications deemed acceptable per protocol specific list of concomitant&#xD;
             medications.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hanmi pharma</name>
      <address>
        <city>Chula Vista</city>
        <state>California</state>
        <zip>91911</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>November 5, 2012</study_first_submitted>
  <study_first_submitted_qc>November 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 12, 2012</study_first_posted>
  <last_update_submitted>November 7, 2017</last_update_submitted>
  <last_update_submitted_qc>November 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</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/NCT01724814
org study id: HM-INS-101
nct id: NCT01724814
lead sponsor: 
has dmc: No
Study Design:

      Part 1.Randomized, double-blind, placebo-controlled, escalating single-dose design with
      Healthy volunteers Part 2.Open , sequential, two-period, single dose study with type 1
      diabetes Part 3.Open, sequential, two-period, single dose study with type 2 diabetes
The principle objectives of this study are to assess safety and tolerability and to explore
      pharmacokinetic(PK) and pharmacodynamic(PD) parameters of a single dose of a novel very-long
      acting insulin formulation (HM12460A) in comparison to a single dose of human Neutral
      Protamine Hagedorn (NPH) in healthy volunteers (part 1), subjects with type 1 diabetes (part
      2) and in subjects with type 2 diabetes (part 3).

      The study will incorporate adaptive elements to provide both PK and PD data. The dose of
      HM12460A to be administered to the subjects with type 1 diabetes and type 2 diabetes will be
      guided by PK data from part 1 of the study; the PD assessment of HM12460A in subjects with
      diabetes will also be informed by knowledge of PK gained from the healthy volunteer study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Incidence and severity of treatment emergent adverse events
time frame: one year
measure: Peak Plasma Concentration(Cmax) of HM12460A following a single dose in Parts 1-3
time frame: one year
description: PK properties of HM12460A following a single dose in Parts 1-3 will be assessed in plasma using a validated assay
arm group label: Cohort S1
arm group type: Experimental
description: HM12460A Dose 1 (1.2 nmol/kg) or placebo
arm group label: Cohort S2
arm group type: Experimental
description: HM12460A Dose 2 (2.4 nmol/kg) or Placebo
arm group label: Cohort S3
arm group type: Experimental
description: HM12460A Dose 3 (4.8 nmol/kg) or Placebo
arm group label: Cohort S4
arm group type: Experimental
description: HM12460A Dose 4 (9.6 nmol/kg) or Placebo
arm group label: Cohort S5
arm group type: Experimental
description: HM12460A Dose 5 (14.4 nmol/kg) or Placebo
arm group label: Cohort S6
arm group type: Experimental
description: HM12460A Dose 6 (19.2 nmol/kg) or Placebo
intervention type: Drug
intervention name: HM12460A
description: Single dose SC administration ranging from 1.2 nmol/kg to 19.2 nmol/kg of HM12460A
arm group label: Cohort S1
arm group label: Cohort S2
arm group label: Cohort S3
arm group label: Cohort S4
arm group label: Cohort S5
arm group label: Cohort S6
other name: LAPS-Insulin
intervention type: Drug
intervention name: Placebo
description: Singe dose SC administration of Placebo
arm group label: Cohort S1
arm group label: Cohort S2
arm group label: Cohort S3
arm group label: Cohort S4
arm group label: Cohort S5
arm group label: Cohort S6
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin