<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/NCT02202603</url>
  </required_header>
  <id_info>
    <org_study_id>0020-11-HMO-EnteraBio</org_study_id>
    <nct_id>NCT02202603</nct_id>
  </id_info>
  <brief_title>A Three Stage, Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of Oral PTH (1-34) in Healthy Subjects</brief_title>
  <official_title>A Three Stage, Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of Oral PTH (1-34) in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Entera Bio Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Entera Bio Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Double blinded (oral), Open Label, Study to Assess the Safety, Pharmacokinetics and&#xD;
      Pharmacodynamics of Oral PTH (1-34) in healthy Subjects to establish the safety,&#xD;
      tolerability, bioavailability, pharmacokinetic, and pharmacodynamic profile and the of&#xD;
      Entera's oral PTH(1 - 34) in adult healthy human volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will have three stages. Stage 1: Safety and initial bioavailability of Entera's&#xD;
      oral EP101 in adult male healthy volunteers. (SA-BA) Stage 2: Assessment of bioavailability&#xD;
      and safety of Entera's oral EP101 in adult male healthy volunteers. (SA-BA-PK-PD) Stage 3:&#xD;
      Safety, PK, and PD of final dose of Entera's oral PTH(1 - 34) in adult healthy male and&#xD;
      female volunteers. (SA-BA-PK-PD)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2011</start_date>
  <completion_date type="Actual">August 2013</completion_date>
  <primary_completion_date type="Actual">August 2013</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse events</measure>
    <time_frame>up to 17 weeks</time_frame>
    <description>throughout the study beginning from the time the subject signs the consent form until the end of study, subjects will complete the following evaluations:&#xD;
Vital signs (blood pressure, heart rate, oral temperature)&#xD;
Clinical laboratory evaluations, hematology, chemistry&#xD;
Physical Exam&#xD;
ECG</description>
  </primary_outcome>
  <number_of_arms>13</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Drug Safety</condition>
  <arm_group>
    <arm_group_label>Teriparatide group 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subcutaneous injection of Teriparatide</description>
  </arm_group>
  <arm_group>
    <arm_group_label>excipients</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral pill without API</description>
  </arm_group>
  <arm_group>
    <arm_group_label>API</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of pill with API</description>
  </arm_group>
  <arm_group>
    <arm_group_label>API optimization 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of pill with API, for PK optimization #1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>API optimization 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of pill with API, for PK optimization #2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>API optimization 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of pill with API, for PK optimization #3</description>
  </arm_group>
  <arm_group>
    <arm_group_label>API optimization 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of pill with API, for PK optimization #4</description>
  </arm_group>
  <arm_group>
    <arm_group_label>API optimization 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of pill with API, for PK optimization #5</description>
  </arm_group>
  <arm_group>
    <arm_group_label>API optimization 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of pill with API, for PK optimization #6</description>
  </arm_group>
  <arm_group>
    <arm_group_label>API optimization 7</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of pill with API, for PK optimization #7</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Teriparatide group 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subcutaneous injection of Teriparatide</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Excipients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral pill without API</description>
  </arm_group>
  <arm_group>
    <arm_group_label>API Optimized</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>expanded group size with API in optimized dosage and administration form.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Teriparatide</intervention_name>
    <description>single oral tablet</description>
    <arm_group_label>API</arm_group_label>
    <arm_group_label>API Optimized</arm_group_label>
    <arm_group_label>API optimization 1</arm_group_label>
    <arm_group_label>API optimization 2</arm_group_label>
    <arm_group_label>API optimization 3</arm_group_label>
    <arm_group_label>API optimization 4</arm_group_label>
    <arm_group_label>API optimization 5</arm_group_label>
    <arm_group_label>API optimization 6</arm_group_label>
    <arm_group_label>API optimization 7</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Teriparatide</intervention_name>
    <description>subcutaneous standard injection</description>
    <arm_group_label>Teriparatide group 1</arm_group_label>
    <arm_group_label>Teriparatide group 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Oral placebo</description>
    <arm_group_label>Excipients</arm_group_label>
    <arm_group_label>excipients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ● Signed Informed consent to the study.&#xD;
&#xD;
               -  Male and female volunteers ,aged 18 - 50 years, BMI 18-30 kg/m2, inclusive,&#xD;
&#xD;
               -  Subjects able to adhere to the visit schedule and protocol requirements&#xD;
&#xD;
               -  Hematology ,Chemistry and Urinalysis values with no clinical significance or do&#xD;
                  not reflect a medical condition which according to the physicians' judgment might&#xD;
                  confound the results of the study or pose additional risk to the subject by&#xD;
                  participation in the study.&#xD;
&#xD;
               -  Hemoglobin level &gt;. 12.5 g/dl&#xD;
&#xD;
               -  Blood pressure levels with no clinical significance.&#xD;
&#xD;
               -  Negative serology to HIV, Hepatitis B, Hepatitis C.&#xD;
&#xD;
               -  No known drug and alcohol abuse&#xD;
&#xD;
               -  Negative urinary drugs of abuse at screening&#xD;
&#xD;
               -  No allergy to soy bean products.&#xD;
&#xD;
               -  No prescription medications taken within one month to enrollment&#xD;
&#xD;
               -  Over-the-counter drugs (including vitamins) taken within 14 days prior to visit 2&#xD;
                  are subject to the investigators' discretion for inclusion.&#xD;
&#xD;
               -  No subjects with previous urolithiasis.&#xD;
&#xD;
               -  Non-smoking,&#xD;
&#xD;
               -  In good health as determined by past medical history, physical examination, vital&#xD;
                  signs, electrocardiogram and laboratory tests at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ● Concurrent therapy that, in the Investigator's opinion, would interfere with the&#xD;
             evaluation of the safety or efficacy of the study medication.&#xD;
&#xD;
               -  Treatment with any investigational product within the last 30 days, enrollment or&#xD;
                  intention to enroll in any active study involving the use of investigational&#xD;
                  devices or drugs.&#xD;
&#xD;
               -  Presence of any other condition or circumstance that, in the judgment of the&#xD;
                  Investigator, might increase the risk to the patient or decrease the chance of&#xD;
                  obtaining satisfactory data to achieve the objectives of the study.&#xD;
&#xD;
               -  Active infections&#xD;
&#xD;
               -  History of drug or alcohol abuse&#xD;
&#xD;
               -  Known allergies or sensitivities to components of study treatment or study&#xD;
                  procedures, including Soy.&#xD;
&#xD;
               -  Clinically diagnosed psychiatric disorders that may interfere with patient study&#xD;
                  participation&#xD;
&#xD;
               -  Medical history known or suspected to increase risks of AEs related to study&#xD;
                  drug, up to the investigator's discretion&#xD;
&#xD;
               -  Chronic illnesses, up to the investigator's discretion&#xD;
&#xD;
               -  Female subjects must have a negative serum pregnancy test at screening and be&#xD;
                  willing and able to use a medically acceptable method of birth control&#xD;
                  (non-hormonal intrauterine device with condom, or diaphragm with condom, or&#xD;
                  condom with spermicide) from the screening visit through the study termination&#xD;
                  visit or declare that they are abstaining from sexual intercourse from the&#xD;
                  screening visit through the study termination visit or are surgically sterile&#xD;
                  (have undergone bilateral tubal ligation, bilateral oophorectomy, or&#xD;
                  hysterectomy) or post menopausal. Postmenopausal women are defined as women with&#xD;
                  menstruation cessation for 12 consecutive months prior to signing of the informed&#xD;
                  consent form.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yosef Caraco, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hadassah Ein Kerem Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>HMO Clinical Research Center Hadassah Ein Kerem Medical Center</name>
      <address>
        <city>Jerusalem</city>
        <zip>91120,</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>October 2015</verification_date>
  <study_first_submitted>June 20, 2011</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <last_update_submitted>October 6, 2015</last_update_submitted>
  <last_update_submitted_qc>October 6, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 7, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Teriparatide</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/NCT02202603
org study id: 0020-11-HMO-EnteraBio
nct id: NCT02202603
lead sponsor: 
has dmc: Yes
A Double blinded (oral), Open Label, Study to Assess the Safety, Pharmacokinetics and
      Pharmacodynamics of Oral PTH (1-34) in healthy Subjects to establish the safety,
      tolerability, bioavailability, pharmacokinetic, and pharmacodynamic profile and the of
      Entera's oral PTH(1 - 34) in adult healthy human volunteers.
This study will have three stages. Stage 1: Safety and initial bioavailability of Entera's
      oral EP101 in adult male healthy volunteers. (SA-BA) Stage 2: Assessment of bioavailability
      and safety of Entera's oral EP101 in adult male healthy volunteers. (SA-BA-PK-PD) Stage 3:
      Safety, PK, and PD of final dose of Entera's oral PTH(1 - 34) in adult healthy male and
      female volunteers. (SA-BA-PK-PD)
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Adverse events
time frame: up to 17 weeks
description: throughout the study beginning from the time the subject signs the consent form until the end of study, subjects will complete the following evaluations:
Vital signs (blood pressure, heart rate, oral temperature)
Clinical laboratory evaluations, hematology, chemistry
Physical Exam
ECG
arm group label: Teriparatide group 1
arm group type: Active Comparator
description: Subcutaneous injection of Teriparatide
arm group label: excipients
arm group type: Placebo Comparator
description: Oral pill without API
arm group label: API
arm group type: Experimental
description: Oral administration of pill with API
arm group label: API optimization 1
arm group type: Experimental
description: Oral administration of pill with API, for PK optimization #1
arm group label: API optimization 2
arm group type: Experimental
description: Oral administration of pill with API, for PK optimization #2
arm group label: API optimization 3
arm group type: Experimental
description: Oral administration of pill with API, for PK optimization #3
arm group label: API optimization 4
arm group type: Experimental
description: Oral administration of pill with API, for PK optimization #4
arm group label: API optimization 5
arm group type: Experimental
description: Oral administration of pill with API, for PK optimization #5
arm group label: API optimization 6
arm group type: Experimental
description: Oral administration of pill with API, for PK optimization #6
arm group label: API optimization 7
arm group type: Experimental
description: Oral administration of pill with API, for PK optimization #7
arm group label: Teriparatide group 2
arm group type: Active Comparator
description: Subcutaneous injection of Teriparatide
arm group label: Excipients
arm group type: Experimental
description: Oral pill without API
arm group label: API Optimized
arm group type: Experimental
description: expanded group size with API in optimized dosage and administration form.
intervention type: Drug
intervention name: Teriparatide
description: single oral tablet
arm group label: API
arm group label: API Optimized
arm group label: API optimization 1
arm group label: API optimization 2
arm group label: API optimization 3
arm group label: API optimization 4
arm group label: API optimization 5
arm group label: API optimization 6
arm group label: API optimization 7
intervention type: Drug
intervention name: Teriparatide
description: subcutaneous standard injection
arm group label: Teriparatide group 1
arm group label: Teriparatide group 2
intervention type: Drug
intervention name: placebo
description: Oral placebo
arm group label: Excipients
arm group label: excipients
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Yosef Caraco, MD
role: Principal Investigator
affiliation: Hadassah Ein Kerem Medical Center
facility: 
country: Israel
responsible party type: Sponsor
mesh term: Teriparatide