<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/NCT03235219</url>
  </required_header>
  <id_info>
    <org_study_id>CR108339</org_study_id>
    <secondary_id>64565111EDI1002</secondary_id>
    <nct_id>NCT03235219</nct_id>
  </id_info>
  <brief_title>A Phase 1b Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of JNJ-64565111 in Participants With Type 2 Diabetes Mellitus</brief_title>
  <official_title>A Double-Blind, Randomized, Placebo-Controlled, Multiple Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-64565111 in Men and Women With Type 2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</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>
      The purpose of this Phase 1b study is to assess the safety and tolerability of JNJ-64565111&#xD;
      in adult men and women (of non-child bearing potential) with Type 2 Diabetes Mellitus.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Actual">February 19, 2018</completion_date>
  <primary_completion_date type="Actual">February 19, 2018</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>Up to Day 72</time_frame>
    <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Serum Concentration (Cmax)</measure>
    <time_frame>First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD.</time_frame>
    <description>Maximum observed serum concentration (Cmax) of JNJ-64565111 will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Observed Plasma Concentration (Tmax)</measure>
    <time_frame>First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD</time_frame>
    <description>Actual sampling time to reach maximum observed serum concentration (Tmax) of JNJ-64565111 will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under Concentration-Time Curve From Time Zero to the Last Quantifiable Time (AUC [0-last])</measure>
    <time_frame>First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD)</time_frame>
    <description>The AUC (0-last) of JNJ-64565111 is the area under the serum concentration-time curve from time zero to last quantifiable time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Concentration Over the Dosing Interval Tau (T) at Steady State (Caverage,ss)</measure>
    <time_frame>Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD</time_frame>
    <description>Average concentration over the dosing interval tau at steady state of JNJ-64565111 (defined as area under the serum concentration time curve observed during a dosing interval (tau) at steady state) will be calculated as AUC(0- T)/T.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum Observed Serum Concentration (Cmin)</measure>
    <time_frame>Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD</time_frame>
    <description>Minimum observed serum concentration (Cmin) of JNJ-64565111 will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio</measure>
    <time_frame>First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168 hours PD</time_frame>
    <description>Accumulation ratio of JNJ-64565111, calculated as AUC(0-T), Day 22 / AUC(0-T), Day 1 will be assessed after last dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under Curve over the dosing interval AUC (0-T)</measure>
    <time_frame>Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168 hours PD</time_frame>
    <description>The AUC (0-T) of JNJ-64565111 is the measure of the serum drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Elimination Half-life (t1/2term)</measure>
    <time_frame>Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD</time_frame>
    <description>Apparent terminal elimination half-life of JNJ-64565111, calculated as 0.693/apparent terminal elimination rate constant (Lambda[z]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance (CL/F)</measure>
    <time_frame>Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD</time_frame>
    <description>Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after subcutaneous (SC) dose (apparent SC clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F will be calculated as CL/F = Dose/AUC [0-infinity].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution (V/F)</measure>
    <time_frame>Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD</time_frame>
    <description>Apparent volume of distribution of JNJ-64565111 is based on the terminal phase following subcutaneous administration calculated as Vd/F = Dose/ apparent terminal elimination rate constant (Lambda[z])*AUC [0-infinity].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Rate Constant (Kel)</measure>
    <time_frame>Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD</time_frame>
    <description>Terminal rate constant of JNJ-64565111 is defined as the fraction of drug that is eliminated per unit of time (fraction/hour).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Anti-JNJ-64565111 Antibodies as Measure of Immunogenicity</measure>
    <time_frame>First Dose: Predose (Day 1); Second Dose: predose (Day 8) Third Dose: predose (Day 15); Fourth Dose: predose (Day 22), 144, 480, 720, and 1200 hours post-dose.</time_frame>
    <description>Immunogenicity will be measured by evaluating serum samples collected from participants. Serum samples will be screened for antibodies binding to JNJ-64565111. The titer of confirmed positive samples will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Body Weight</measure>
    <time_frame>Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72</time_frame>
    <description>Body weight will be measured using a calibrated scale at each time a participant is weighed. Calibration must be documented in a calibration log.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Fasting Plasma Glucose (FPG)</measure>
    <time_frame>Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72</time_frame>
    <description>Change from baseline in fasting plasma glucose (FPG) will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hemoglobin A1c (HbA1c)</measure>
    <time_frame>Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72</time_frame>
    <description>Change from baseline in HbA1c will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Fasting Lipids</measure>
    <time_frame>Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72</time_frame>
    <description>Fasting plasma lipids were measured to determine the total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol, very low-density lipoprotein cholesterol (VLDL-C), triglycerides and free fatty acids to understand the potential impact of study drug on cardiovascular disease risk.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline for 24-hour Mean Plasma Glucose</measure>
    <time_frame>Baseline, Day 26</time_frame>
    <description>Mean plasma glucose defined as the total and/or incremental (that is, baseline-subtracted) area under the concentration (AUC) time curve over 0 to 24 hours, divided by 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in C-peptide Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)</measure>
    <time_frame>Baseline, Day 26</time_frame>
    <description>MMTT-Stimulated 6-Hour C-peptide AUC is the mean area under the C-peptide level-time curve over the 6-hour period divided by the duration after a mixed-meal tolerance test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Total and/or Incremental Plasma Glucose Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)</measure>
    <time_frame>Baseline, Day 26</time_frame>
    <description>MMTT-Stimulated 6-Hour total and/or incremental plasma glucose AUC is the mean area under the total and/or incremental plasma glucose level-time curve over the 6-hour period divided by the duration after a mixed-meal tolerance test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Insulin Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)</measure>
    <time_frame>Baseline, Day 26</time_frame>
    <description>MMTT-Stimulated 6-Hour Insulin AUC is the mean area under the insulin level-time curve over the 6-hour period divided by the duration after a mixed-meal tolerance test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Glucagon Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)</measure>
    <time_frame>Baseline, Day 26</time_frame>
    <description>MMTT-Stimulated 6-Hour Glucagon AUC is the mean area under the glucagon level-time curve over the 6-hour period divided by the duration after a mixed-meal tolerance test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in 24-hour Blood Pressure</measure>
    <time_frame>Baseline and Day 28</time_frame>
    <description>Blood Pressure will be assessed by 24-hour ambulatory blood pressure and heart rate monitoring (ABPM) device by periodic measurements performed at 1 hour intervals for the first 14 hours, then at 2-hour intervals for the remaining 10 hours (that is, 19 measurements in total).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in 24-hour Heart Rate</measure>
    <time_frame>Baseline and Day 28</time_frame>
    <description>Heart rate measurements will be assessed with a completely automated (ambulatory blood pressure and heart rate monitoring) device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Body Mass Index (BMI)</measure>
    <time_frame>Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72</time_frame>
    <description>Body Mass Index (BMI) is calculated by dividing the body weight (in kilogram) by the square of height (in meters).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline Insulin Secretion as Assessed by the Insulinogenic Index</measure>
    <time_frame>Baseline, Day 26</time_frame>
    <description>Insulin secretion will be assessed by the insulinogenic index (Insulin 30-Insulin 0)/(Glucose 30-Glucose 0), by measuring the ratio of insulin to glucose. The insulinogenic index is frequently used as a measure of beta cell function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Insulin Secretion as Assessed by Homeostasis Model Assessment of Beta Cell Function (HOMA-%B)</measure>
    <time_frame>Baseline, Day 26</time_frame>
    <description>HOMA is used to quantify insulin resistance and beta-cell function from basal (fasting) glucose and insulin (or C-peptide) concentrations. HOMA-B will be calculated by 20*I/(G-3.5) where I is fasting plasma insulin (micro units/per milliliter [uU/mL]) and G is fasting plasma glucose (millimoles per liter [mmol/L]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Insulin Sensitivity as Assessed by Matsuda Index</measure>
    <time_frame>Baseline, Day 26</time_frame>
    <description>The Matsuda index represents a composite of both hepatic and peripheral tissue sensitivity to insulin. Insulin sensitivity by Matsuda Index will be calculated by (10,000/square root of [fasting glucose * fasting insulin] * [mean glucose * mean insulin during oral glucose tolerance test [OGTT]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Insulin Sensitivity as Assessed by Homeostasis Model Assessment for Insulin Sensitivity (HOMA-%S)</measure>
    <time_frame>Baseline, Day 26</time_frame>
    <description>Insulin sensitivity will be assessed by Homeostasis Model Assessment (HOMA-%S) where HOMA-%S is 100/HOMA-Insulin Resistance [IR]. The HOMA-IR is the product of the blood Glucose and Insulin levels, divided by a constant. HOMA-IR is expressed as the following: HOMA-IR = fasting serum insulin (uU/mL) * fasting plasma glucose (mmol/L) / 22.5.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Cohort 1 to 4: JNJ-64565111 or Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in cohort 1 to 4 in a ratio of 4:1 will receive a dose of JNJ-64565111 or placebo subcutaneously on Days 1, 8, 15 and 22. Cohort 1, 2 and 3 will be dosed in parallel. Dosing for subsequent cohort 4 will be escalated based on review by the Sponsor and Principal Investigator of blinded safety, tolerability, pharmacokinetic, and (all available) pharmacodynamic data collected up to Day 29, but will not exceed from well-tolerated dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 5: JNJ-64565111 (Repeat or Lower Dose) or Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in ratio of 4:1 will receive a dose of JNJ-64565111 or placebo subcutaneously on Days 1, 8, 15 and 22, and may be modified. The dose can be repeated or lower than a dose previously assessed as well tolerated.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>JNJ-64565111</intervention_name>
    <description>Participants will receive JNJ-64565111 subcutaneously in the abdomen on Days 1, 8, 15 and 22.</description>
    <arm_group_label>Cohort 1 to 4: JNJ-64565111 or Placebo</arm_group_label>
    <arm_group_label>Cohort 5: JNJ-64565111 (Repeat or Lower Dose) or Placebo</arm_group_label>
    <other_name>Oxyntomodulin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive placebo subcutaneously in the abdomen on Days 1, 8, 15 and 22.</description>
    <arm_group_label>Cohort 1 to 4: JNJ-64565111 or Placebo</arm_group_label>
    <arm_group_label>Cohort 5: JNJ-64565111 (Repeat or Lower Dose) or Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of type 2 diabetes mellitus (T2DM) at least 3 months prior to Screening&#xD;
&#xD;
          -  Hemoglobin A1c (HbA1c) greater than or equal to (&gt;=) 7.0 percent (%) and lesser than&#xD;
             or equal to (&lt;=)9.5% at Screening&#xD;
&#xD;
          -  On a stable treatment regimen for at least 3 months prior to Screening of (1) diet and&#xD;
             exercise, and/or (2) metformin monotherapy (at a dose of at least 1,000 milligram (mg)&#xD;
             per day)&#xD;
&#xD;
          -  Body mass index (BMI) ranging from 25 to 40 kilogram per square meter (kg/m^2)&#xD;
             (inclusive), weighing between 75 and 130 kg (inclusive)&#xD;
&#xD;
          -  A woman must have a negative highly sensitive serum beta-human chorionic gonadotropin&#xD;
             (beta- hCG) at Screening and Day -2&#xD;
&#xD;
          -  Blood pressure (measured after the participant is sitting/ resting quietly for 5&#xD;
             minutes) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and&#xD;
             between 60 and 100 mmHg diastolic, inclusive at Screening (sitting) and Day -2&#xD;
             (supine). If the average of the first triplicate blood pressure assessment is out of&#xD;
             range, up to 2 repeated triplicate assessments are permitted&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History or current diagnosis of acute or chronic pancreatitis&#xD;
&#xD;
          -  Familial or personal history of multiple endocrine neoplasia type&#xD;
             2,familial/non-familial medullary thyroid carcinoma&#xD;
&#xD;
          -  Donated blood or blood products or lost a significant amount of blood (&gt;500 milliliter&#xD;
             [mL]) within 3 months before the first administration of study drug&#xD;
&#xD;
          -  History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV)&#xD;
             positive, or other clinically active liver disease, or tests positive for HBsAg or&#xD;
             anti-HCV at Screening&#xD;
&#xD;
          -  History of human immunodeficiency virus (HIV) antibody positive, or tests positive for&#xD;
             HIV at Screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ProSciento, Inc.</name>
      <address>
        <city>Chula Vista</city>
        <state>California</state>
        <zip>91911</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Pharma CR, LLC</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33147</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 28, 2017</study_first_submitted>
  <study_first_submitted_qc>July 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 1, 2017</study_first_posted>
  <last_update_submitted>April 13, 2023</last_update_submitted>
  <last_update_submitted_qc>April 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2023</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 2</mesh_term>
  </condition_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/NCT03235219
org study id: CR108339
secondary id: 64565111EDI1002
nct id: NCT03235219
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this Phase 1b study is to assess the safety and tolerability of JNJ-64565111
      in adult men and women (of non-child bearing potential) with Type 2 Diabetes Mellitus.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
time frame: Up to Day 72
description: An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
measure: Maximum Observed Serum Concentration (Cmax)
time frame: First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD.
description: Maximum observed serum concentration (Cmax) of JNJ-64565111 will be assessed.
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
time frame: First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
description: Actual sampling time to reach maximum observed serum concentration (Tmax) of JNJ-64565111 will be assessed.
measure: Area Under Concentration-Time Curve From Time Zero to the Last Quantifiable Time (AUC [0-last])
time frame: First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD)
description: The AUC (0-last) of JNJ-64565111 is the area under the serum concentration-time curve from time zero to last quantifiable time.
measure: Average Concentration Over the Dosing Interval Tau (T) at Steady State (Caverage,ss)
time frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
description: Average concentration over the dosing interval tau at steady state of JNJ-64565111 (defined as area under the serum concentration time curve observed during a dosing interval (tau) at steady state) will be calculated as AUC(0- T)/T.
measure: Minimum Observed Serum Concentration (Cmin)
time frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
description: Minimum observed serum concentration (Cmin) of JNJ-64565111 will be assessed.
measure: Accumulation Ratio
time frame: First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168 hours PD
description: Accumulation ratio of JNJ-64565111, calculated as AUC(0-T), Day 22 / AUC(0-T), Day 1 will be assessed after last dose.
measure: Area Under Curve over the dosing interval AUC (0-T)
time frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168 hours PD
description: The AUC (0-T) of JNJ-64565111 is the measure of the serum drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
measure: Apparent Terminal Elimination Half-life (t1/2term)
time frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
description: Apparent terminal elimination half-life of JNJ-64565111, calculated as 0.693/apparent terminal elimination rate constant (Lambda[z]).
measure: Apparent Clearance (CL/F)
time frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
description: Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after subcutaneous (SC) dose (apparent SC clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F will be calculated as CL/F = Dose/AUC [0-infinity].
measure: Apparent Volume of Distribution (V/F)
time frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
description: Apparent volume of distribution of JNJ-64565111 is based on the terminal phase following subcutaneous administration calculated as Vd/F = Dose/ apparent terminal elimination rate constant (Lambda[z])*AUC [0-infinity].
measure: Terminal Rate Constant (Kel)
time frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
description: Terminal rate constant of JNJ-64565111 is defined as the fraction of drug that is eliminated per unit of time (fraction/hour).
measure: Number of Participants With Anti-JNJ-64565111 Antibodies as Measure of Immunogenicity
time frame: First Dose: Predose (Day 1); Second Dose: predose (Day 8) Third Dose: predose (Day 15); Fourth Dose: predose (Day 22), 144, 480, 720, and 1200 hours post-dose.
description: Immunogenicity will be measured by evaluating serum samples collected from participants. Serum samples will be screened for antibodies binding to JNJ-64565111. The titer of confirmed positive samples will be reported.
measure: Change From Baseline in Body Weight
time frame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
description: Body weight will be measured using a calibrated scale at each time a participant is weighed. Calibration must be documented in a calibration log.
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
time frame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
description: Change from baseline in fasting plasma glucose (FPG) will be assessed.
measure: Change From Baseline in Hemoglobin A1c (HbA1c)
time frame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
description: Change from baseline in HbA1c will be assessed.
measure: Change From Baseline in Fasting Lipids
time frame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
description: Fasting plasma lipids were measured to determine the total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol, very low-density lipoprotein cholesterol (VLDL-C), triglycerides and free fatty acids to understand the potential impact of study drug on cardiovascular disease risk.
measure: Change From Baseline for 24-hour Mean Plasma Glucose
time frame: Baseline, Day 26
description: Mean plasma glucose defined as the total and/or incremental (that is, baseline-subtracted) area under the concentration (AUC) time curve over 0 to 24 hours, divided by 24.
measure: Change From Baseline in C-peptide Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)
time frame: Baseline, Day 26
description: MMTT-Stimulated 6-Hour C-peptide AUC is the mean area under the C-peptide level-time curve over the 6-hour period divided by the duration after a mixed-meal tolerance test.
measure: Change From Baseline in Total and/or Incremental Plasma Glucose Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)
time frame: Baseline, Day 26
description: MMTT-Stimulated 6-Hour total and/or incremental plasma glucose AUC is the mean area under the total and/or incremental plasma glucose level-time curve over the 6-hour period divided by the duration after a mixed-meal tolerance test.
measure: Change From Baseline in Insulin Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)
time frame: Baseline, Day 26
description: MMTT-Stimulated 6-Hour Insulin AUC is the mean area under the insulin level-time curve over the 6-hour period divided by the duration after a mixed-meal tolerance test.
measure: Change From Baseline in Glucagon Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)
time frame: Baseline, Day 26
description: MMTT-Stimulated 6-Hour Glucagon AUC is the mean area under the glucagon level-time curve over the 6-hour period divided by the duration after a mixed-meal tolerance test.
measure: Change From Baseline in 24-hour Blood Pressure
time frame: Baseline and Day 28
description: Blood Pressure will be assessed by 24-hour ambulatory blood pressure and heart rate monitoring (ABPM) device by periodic measurements performed at 1 hour intervals for the first 14 hours, then at 2-hour intervals for the remaining 10 hours (that is, 19 measurements in total).
measure: Change From Baseline in 24-hour Heart Rate
time frame: Baseline and Day 28
description: Heart rate measurements will be assessed with a completely automated (ambulatory blood pressure and heart rate monitoring) device.
measure: Change From Baseline in Body Mass Index (BMI)
time frame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
description: Body Mass Index (BMI) is calculated by dividing the body weight (in kilogram) by the square of height (in meters).
measure: Change From Baseline Insulin Secretion as Assessed by the Insulinogenic Index
time frame: Baseline, Day 26
description: Insulin secretion will be assessed by the insulinogenic index (Insulin 30-Insulin 0)/(Glucose 30-Glucose 0), by measuring the ratio of insulin to glucose. The insulinogenic index is frequently used as a measure of beta cell function.
measure: Change from Baseline in Insulin Secretion as Assessed by Homeostasis Model Assessment of Beta Cell Function (HOMA-%B)
time frame: Baseline, Day 26
description: HOMA is used to quantify insulin resistance and beta-cell function from basal (fasting) glucose and insulin (or C-peptide) concentrations. HOMA-B will be calculated by 20*I/(G-3.5) where I is fasting plasma insulin (micro units/per milliliter [uU/mL]) and G is fasting plasma glucose (millimoles per liter [mmol/L]).
measure: Change From Baseline in Insulin Sensitivity as Assessed by Matsuda Index
time frame: Baseline, Day 26
description: The Matsuda index represents a composite of both hepatic and peripheral tissue sensitivity to insulin. Insulin sensitivity by Matsuda Index will be calculated by (10,000/square root of [fasting glucose * fasting insulin] * [mean glucose * mean insulin during oral glucose tolerance test [OGTT]).
measure: Change From Baseline in Insulin Sensitivity as Assessed by Homeostasis Model Assessment for Insulin Sensitivity (HOMA-%S)
time frame: Baseline, Day 26
description: Insulin sensitivity will be assessed by Homeostasis Model Assessment (HOMA-%S) where HOMA-%S is 100/HOMA-Insulin Resistance [IR]. The HOMA-IR is the product of the blood Glucose and Insulin levels, divided by a constant. HOMA-IR is expressed as the following: HOMA-IR = fasting serum insulin (uU/mL) * fasting plasma glucose (mmol/L) / 22.5.
arm group label: Cohort 1 to 4: JNJ-64565111 or Placebo
arm group type: Experimental
description: Participants in cohort 1 to 4 in a ratio of 4:1 will receive a dose of JNJ-64565111 or placebo subcutaneously on Days 1, 8, 15 and 22. Cohort 1, 2 and 3 will be dosed in parallel. Dosing for subsequent cohort 4 will be escalated based on review by the Sponsor and Principal Investigator of blinded safety, tolerability, pharmacokinetic, and (all available) pharmacodynamic data collected up to Day 29, but will not exceed from well-tolerated dose.
arm group label: Cohort 5: JNJ-64565111 (Repeat or Lower Dose) or Placebo
arm group type: Experimental
description: Participants in ratio of 4:1 will receive a dose of JNJ-64565111 or placebo subcutaneously on Days 1, 8, 15 and 22, and may be modified. The dose can be repeated or lower than a dose previously assessed as well tolerated.
intervention type: Drug
intervention name: JNJ-64565111
description: Participants will receive JNJ-64565111 subcutaneously in the abdomen on Days 1, 8, 15 and 22.
arm group label: Cohort 1 to 4: JNJ-64565111 or Placebo
arm group label: Cohort 5: JNJ-64565111 (Repeat or Lower Dose) or Placebo
other name: Oxyntomodulin
intervention type: Drug
intervention name: Placebo
description: Participants will receive placebo subcutaneously in the abdomen on Days 1, 8, 15 and 22.
arm group label: Cohort 1 to 4: JNJ-64565111 or Placebo
arm group label: Cohort 5: JNJ-64565111 (Repeat or Lower Dose) or Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2