<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/NCT01666691</url>
  </required_header>
  <id_info>
    <org_study_id>ZAF-201</org_study_id>
    <nct_id>NCT01666691</nct_id>
  </id_info>
  <brief_title>An Efficacy, Safety and Pharmacokinetics Study of Beloranib (ZGN-440 for Injectable Suspension) in Obese Subjects</brief_title>
  <official_title>Randomized, Double-Blind, Placebo Controlled, Dose Ranging Phase 2 Trial of Beloranib (ZGN-440 for Injectable Suspension), A Novel Methionine Aminopeptidase 2 Inhibitor, in Obese Subjects to Evaluate Weight Reduction, Safety, and Pharmacokinetics Over 12 Weeks</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zafgen, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zafgen, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate weight reduction, safety and pharmacokinetics for&#xD;
      certain doses of beloranib (ZGN-440 for injectable suspension) administered as twice-weekly&#xD;
      subcutaneous injections for 12 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This protocol is designed to test the safety and efficacy of a drug called beloranib (ZGN-440&#xD;
      for injectable suspension). It is to be tested for its ability to reduce weight in obese&#xD;
      subjects. The study will provide information on how much ZGN-440 gets into the blood, how&#xD;
      long it stays in the body, and how it affects other biological markers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">May 2013</completion_date>
  <primary_completion_date type="Actual">May 2013</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability of beloranib (ZGN-440 for injectable suspension) administered subcutaneously for 12 weeks</measure>
    <time_frame>Up to 26 weeks</time_frame>
    <description>Safety and tolerability of beloranib will be assessed by comparing frequency and severity of adverse events as well as changes in physical examinations, ECGs, vital signs and laboratory evaluations. Other safety oriented questionnaires and parameters (e.g. sleep quality, hemodynamic parameters) will be measured and evaluated.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Weight loss and responses in metabolic biomarkers over a dose range of ZGN-440</measure>
    <time_frame>Up to 13 weeks</time_frame>
    <description>Change from baseline in body weight and body composition (bioimpedance assessments), and scores of hunger/appetite over the dosing period will be evaluated to document beloranib's effect on obesity. Biomarkers of lipid metabolism will be measured to assess possible mechanisms of loss of body fat, as well as endocrinologic or anti-inflammatory markers.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics over a dose range of beloranib</measure>
    <time_frame>Up to 12 weeks</time_frame>
    <description>The plasma PK of beloranib and selected metabolites may be assessed following dose administration to compare systemic exposure and PK parameters over the range of doses. PK parameters include Cmax, Tmax, AUC24hour, AUC∞, volume of distribution, total clearance, terminal elimination constant, and half-life. Mean residence time may also be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the plasma pharmacokinetic profile of beloranib administered subcutaneously with the profiles obtained previously using an alternative formulation administered subcutaneously and with ZGN-433 (beloranib hemioxalate) administered intravenously</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent bioavailability over a dose range of beloranib</measure>
    <time_frame>Up to 12 weeks</time_frame>
    <description>Bioavailability will be estimated from the SC PK parameters compared to the profile from comparable doses in earlier IV administration studies.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">160</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>ZGN-440 sterile diluent</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.3 mg Beloranib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.3 mg ZGN-440 for injectable suspension</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.6 mg Beloranib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.6 mg ZGN-440 for injectable suspension</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1.2 mg Beloranib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1.2 mg ZGN-440 for injectable suspension</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2.4 mg Beloranib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2.4 mg ZGN-440 for injectable suspension</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3.2 mg Beloranib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3.2 mg ZGN-440 for injectable suspension</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Beloranib</intervention_name>
    <description>Subjects will receive ZGN-440 twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses. A range of doses will be evaluated.</description>
    <arm_group_label>0.3 mg Beloranib</arm_group_label>
    <arm_group_label>0.6 mg Beloranib</arm_group_label>
    <arm_group_label>1.2 mg Beloranib</arm_group_label>
    <arm_group_label>2.4 mg Beloranib</arm_group_label>
    <arm_group_label>3.2 mg Beloranib</arm_group_label>
    <other_name>ZGN-440 for injectable suspension</other_name>
    <other_name>ZGN-440</other_name>
    <other_name>ZGN-433</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects will receive placebo twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>ZGN-440 sterile diluent</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Obese volunteers weighing ≥ 50 kg&#xD;
&#xD;
          -  BMI ≥ 30 and ≤ 50 kg/m2&#xD;
&#xD;
          -  Stable body weight during the past 2 months&#xD;
&#xD;
          -  Type 2 diabetes mellitus is allowed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of weight loss agents in the past month&#xD;
&#xD;
          -  Current, clinically significant eating disorder&#xD;
&#xD;
          -  Type 1 diabetes mellitus&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>J K Marjason, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Q-Pharm Clinics, Royal Brisbane and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Q-Pharm Clinics, Royal Brisbane and Women's Hospital</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CMAX</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linear Clinical Research Ltd</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>July 2016</verification_date>
  <study_first_submitted>August 8, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>July 13, 2016</last_update_submitted>
  <last_update_submitted_qc>July 13, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 14, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Obese</keyword>
  <keyword>Obesity</keyword>
  <keyword>Overweight</keyword>
  <keyword>Weight loss</keyword>
  <keyword>Weight reduction</keyword>
  <keyword>Beloranib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>CKD732</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/NCT01666691
org study id: ZAF-201
nct id: NCT01666691
lead sponsor: 
has dmc: Yes
The purpose of this study is to evaluate weight reduction, safety and pharmacokinetics for
      certain doses of beloranib (ZGN-440 for injectable suspension) administered as twice-weekly
      subcutaneous injections for 12 weeks.
This protocol is designed to test the safety and efficacy of a drug called beloranib (ZGN-440
      for injectable suspension). It is to be tested for its ability to reduce weight in obese
      subjects. The study will provide information on how much ZGN-440 gets into the blood, how
      long it stays in the body, and how it affects other biological markers.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Safety and tolerability of beloranib (ZGN-440 for injectable suspension) administered subcutaneously for 12 weeks
time frame: Up to 26 weeks
description: Safety and tolerability of beloranib will be assessed by comparing frequency and severity of adverse events as well as changes in physical examinations, ECGs, vital signs and laboratory evaluations. Other safety oriented questionnaires and parameters (e.g. sleep quality, hemodynamic parameters) will be measured and evaluated.
measure: Weight loss and responses in metabolic biomarkers over a dose range of ZGN-440
time frame: Up to 13 weeks
description: Change from baseline in body weight and body composition (bioimpedance assessments), and scores of hunger/appetite over the dosing period will be evaluated to document beloranib's effect on obesity. Biomarkers of lipid metabolism will be measured to assess possible mechanisms of loss of body fat, as well as endocrinologic or anti-inflammatory markers.
measure: Pharmacodynamics over a dose range of beloranib
time frame: Up to 12 weeks
description: The plasma PK of beloranib and selected metabolites may be assessed following dose administration to compare systemic exposure and PK parameters over the range of doses. PK parameters include Cmax, Tmax, AUC24hour, AUC∞, volume of distribution, total clearance, terminal elimination constant, and half-life. Mean residence time may also be reported.
measure: Compare the plasma pharmacokinetic profile of beloranib administered subcutaneously with the profiles obtained previously using an alternative formulation administered subcutaneously and with ZGN-433 (beloranib hemioxalate) administered intravenously
time frame: Up to 12 weeks
measure: Apparent bioavailability over a dose range of beloranib
time frame: Up to 12 weeks
description: Bioavailability will be estimated from the SC PK parameters compared to the profile from comparable doses in earlier IV administration studies.
arm group label: Placebo
arm group type: Placebo Comparator
description: ZGN-440 sterile diluent
arm group label: 0.3 mg Beloranib
arm group type: Experimental
description: 0.3 mg ZGN-440 for injectable suspension
arm group label: 0.6 mg Beloranib
arm group type: Experimental
description: 0.6 mg ZGN-440 for injectable suspension
arm group label: 1.2 mg Beloranib
arm group type: Experimental
description: 1.2 mg ZGN-440 for injectable suspension
arm group label: 2.4 mg Beloranib
arm group type: Experimental
description: 2.4 mg ZGN-440 for injectable suspension
arm group label: 3.2 mg Beloranib
arm group type: Experimental
description: 3.2 mg ZGN-440 for injectable suspension
intervention type: Drug
intervention name: Beloranib
description: Subjects will receive ZGN-440 twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses. A range of doses will be evaluated.
arm group label: 0.3 mg Beloranib
arm group label: 0.6 mg Beloranib
arm group label: 1.2 mg Beloranib
arm group label: 2.4 mg Beloranib
arm group label: 3.2 mg Beloranib
other name: ZGN-440 for injectable suspension
other name: ZGN-440
other name: ZGN-433
intervention type: Drug
intervention name: Placebo
description: Subjects will receive placebo twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses.
arm group label: Placebo
other name: ZGN-440 sterile diluent
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: J K Marjason, MD
role: Principal Investigator
affiliation: Q-Pharm Clinics, Royal Brisbane and Women's Hospital
facility: 
facility: 
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Obesity
mesh term: CKD732