xml: <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/NCT05965167</url>
    </required_header>
    <id_info>
      <org_study_id>ENT-11-2023</org_study_id>
      <nct_id>NCT05965167</nct_id>
    </id_info>
    <brief_title>Assess Safety and Compare PK of New Oral hPTH(1-34) Tablet Formulations vs. EBP05 Tablets and Subcutaneous Forteo</brief_title>
    <official_title>A Phase 1b, Open-label, Partially Randomised Study to Assess Safety and Compare Pharmacokinetics of New Oral hPTH(1-34) Tablet Formulations vs. Oral EBP05 Tablets and Subcutaneous Forteo® Injection in Healthy Male 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>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to characterize and compare the pharmacokinetics of hPTH(1 34)&#xD;
        after treatment with a modified oral formulation (EBP11, EBP11-M, and EBP22) versus two dose&#xD;
        levels of Entera Bio's extensively studied oral EBP05 1.5 mg and 2.5 mg as well as the&#xD;
        commercial Forteo 0.02 mg subcutaneous injection.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">May 11, 2023</start_date>
    <completion_date type="Anticipated">March 2024</completion_date>
    <primary_completion_date type="Anticipated">March 2024</primary_completion_date>
    <phase>Phase 1/Phase 2</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>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Assessment of the pharmacokinetic profile of plasma hPTH(1-34) after single or twice daily oral administration for treatment regimen as listed under Arms and Interventions at 5, 10, 15, 20, 40, 50, 60, 75, 90, 105, 120, 180, 240, 360 min. post dose</measure>
      <time_frame>6 hours</time_frame>
      <description>Pharmacokinetic parameter - plasma hPTH(1-34) in pg/mL</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Calculation of plasma levels of hPTH(1-34) AUC0-t for each treatment regimen</measure>
      <time_frame>6 hours</time_frame>
      <description>Pharmacokinetic parameter - total drug exposure at different time points up to 360 min. post dose</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Calculation of plasma levels of hPTH(1-34) AUC0-inf for each treatment regimen</measure>
      <time_frame>6-14 hours</time_frame>
      <description>Pharmacokinetic parameter - total drug exposure in pg/mL over time from 0 extrapolated to infinity</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Calculation of plasma levels of hPTH(1-34) AUC%extrap for each treatment regimen</measure>
      <time_frame>6-14 hours</time_frame>
      <description>Pharmacokinetic parameter - Percent of AUC0-inf extrapolated to confirm reliability</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Calculation of plasma levels of hPTH(1-34) Cmax for each treatment regimen</measure>
      <time_frame>6-14 hours</time_frame>
      <description>Pharmacokinetic parameter - hPTH (1-34) maximal concentration in pg/mL (Cmax)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Calculation of plasma levels of hPTH(1-34) Tmax for each treatment regimen</measure>
      <time_frame>6-14 hours</time_frame>
      <description>Pharmacokinetic parameter - time in minutes to reach max. concentration of hPTH(1-34)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Calculation of plasma levels of hPTH(1-34) Kel for each treatment regimen</measure>
      <time_frame>6 hours</time_frame>
      <description>Pharmacokinetic parameter - elimination rate constant in pg/mL, fraction of drug eliminated per time-point up to 360 min. post dose</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Calculation of plasma levels of hPTH(1-34) t½ for each treatment regimen</measure>
      <time_frame>6-14 hours</time_frame>
      <description>Pharmacokinetic parameter - terminal elimination half life of hPTH(1-34) in minutes</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Calculation of plasma levels of hPTH(1-34) Tlast for each treatment regimen</measure>
      <time_frame>6-14 hours</time_frame>
      <description>Pharmacokinetic parameter - time of the last measurable concentration of hPTH(1-34) in minutes</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Assessment of inter-subject variability of hPTH(1-34) for each treatment regimen</measure>
      <time_frame>6-14 hours</time_frame>
      <description>Pharmacokinetic parameter - Coefficient of Variance (CV%) of hPTH (1-34)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Calculation of dose proportionality for hPTH(1-34) for relevant treatment regimen</measure>
      <time_frame>6 hours</time_frame>
      <description>Pharmacokinetic parameter</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Assessment of the duration of exposure to hPTH(1-34) in minutes</measure>
      <time_frame>6 hours</time_frame>
      <description>Pharmacokinetic parameter - up to 360 min. post dose</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Vital Signs - body temperature (Celsius)</measure>
      <time_frame>6 hours</time_frame>
      <description>Safety parameter (group mean at each time point up to 360 min. post dose)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Vital Signs - respiratory rate (breaths per minute)</measure>
      <time_frame>6 hours</time_frame>
      <description>Safety parameter (group mean at each time point up to 360 min. post dose)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Vital Signs - blood pressure (systolic/diastolic mmHg)</measure>
      <time_frame>6 hours</time_frame>
      <description>Safety parameter (group mean at each time point up to 360 min. post dose)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Vital Signs - heart rate (beats per minute)</measure>
      <time_frame>6 hours</time_frame>
      <description>Safety parameter (group mean at each time point up to 360 min. post dose)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of Treatment-Emergent Adverse Events as assessed by the Principle Investigator</measure>
      <time_frame>6-14 hours</time_frame>
      <description>Safety parameter - AEs observed over duration of study participation</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of Serious Adverse Events (SAEs) as assessed by the Principle Investigator</measure>
      <time_frame>6-14 hours</time_frame>
      <description>Safety parameter - SAEs observed over duration of study participation</description>
    </primary_outcome>
    <other_outcome>
      <measure>Measurement of plasma soybean trypsin inhibitor, Kunitz type (SBTI) levels (EBP05 only)</measure>
      <time_frame>6 hours</time_frame>
      <description>Pharmacokinetic parameter in ng/mL</description>
    </other_outcome>
    <other_outcome>
      <measure>Measurement of plasma salcaprozate sodium (SNAC) levels (EBP05 only)</measure>
      <time_frame>6 hours</time_frame>
      <description>Pharmacokinetic parameter in μg/mL</description>
    </other_outcome>
    <other_outcome>
      <measure>Measurement of serum calcium (albumin-corrected total calcium) for all treatment regimen</measure>
      <time_frame>6 hours</time_frame>
      <description>Pharmacodynamic parameter in mg/dL at 120, 240, 360 min post dose</description>
    </other_outcome>
    <other_outcome>
      <measure>Measurement of serum phosphate for all treatment regimen</measure>
      <time_frame>6 hours</time_frame>
      <description>Pharmacodynamic parameter in mg/dL at 120, 240, 360 min post dose</description>
    </other_outcome>
    <other_outcome>
      <measure>Measurement of serum intact hPTH(1-84) for all treatment regimen</measure>
      <time_frame>6 hours</time_frame>
      <description>Pharmacodynamic parameter in pg/mL at 120, 240, 360 min post dose</description>
    </other_outcome>
    <other_outcome>
      <measure>Measurement of serum 1,25-(OH)2D for all treatment regimen (optional)</measure>
      <time_frame>6 hours</time_frame>
      <description>Pharmacodynamic parameter in ng/mL at 120, 240, 360 min post dose</description>
    </other_outcome>
    <number_of_arms>14</number_of_arms>
    <enrollment type="Anticipated">45</enrollment>
    <condition>Hypoparathyroidism</condition>
    <arm_group>
      <arm_group_label>Treatment A EBP05 2.5 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single dose of oral EBP05 2.5 mg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment B EBP05 1.5 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single dose of oral EBP05 1.5 mg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment C Forteo 20 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single SC injection of Forteo 0.02 mg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment D EBP11 1.5 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single dose of oral EBP11 1.5 mg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment E EBP11 BID (dose determined after IA)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Based on PK data from 1st Interim Analysis BID administration of oral EBP11. The selected BID dose to be administered will be either 1.5, 2.0 or 2.5 mg.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment F EBP11 BID (dose determined after IA)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>BID administration of oral EBP11 tablets. The selected EBP11 dose will be either 1.5, 2.0 or 2.5 mg based on hPTH(1-34) PK data from the 1st and 2nd Interim Analyses.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment G EBP11 1.5 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single dose of oral EBP11 1.5 mg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment H EBP11-M 1.5 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single dose of oral EBP11-M 1.5 mg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment I EBP22 1.5 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single dose of oral EBP22 1.5 mg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment J EBP22 1.5 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single dose of oral EBP22 1.5 mg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment K oral EBP formulation determined based on IA results</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single dose of oral 1.5 mg of the selected oral formulation (EBP11, EBP11-M, or EBP22) based on the results of all Cohort 1 and 2 Interim Analyses</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment L BID of oral EBP formulation determined based on IA results</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>BID dose of oral 1.5 mg of the selected oral formulation (EBP11, EBP11-M, or EBP22) based on the results of all Cohort 1 and 2 Interim Analyses</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment M BID of EBP05 2.5 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>BID dose of oral EBP05 2.5 mg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment N single dose of Treatment K</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single dose of Treatment K</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>EBP05</intervention_name>
      <description>Oral tablets</description>
      <arm_group_label>Treatment A EBP05 2.5 mg</arm_group_label>
      <arm_group_label>Treatment B EBP05 1.5 mg</arm_group_label>
      <arm_group_label>Treatment M BID of EBP05 2.5 mg</arm_group_label>
      <other_name>hPTH(1-34)</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Forteo 20 mg</intervention_name>
      <description>Subcutaneous injection</description>
      <arm_group_label>Treatment C Forteo 20 mg</arm_group_label>
      <other_name>hPTH(1-34)</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>EBP11</intervention_name>
      <description>Oral tablets</description>
      <arm_group_label>Treatment D EBP11 1.5 mg</arm_group_label>
      <arm_group_label>Treatment E EBP11 BID (dose determined after IA)</arm_group_label>
      <arm_group_label>Treatment F EBP11 BID (dose determined after IA)</arm_group_label>
      <arm_group_label>Treatment G EBP11 1.5 mg</arm_group_label>
      <arm_group_label>Treatment K oral EBP formulation determined based on IA results</arm_group_label>
      <arm_group_label>Treatment L BID of oral EBP formulation determined based on IA results</arm_group_label>
      <arm_group_label>Treatment N single dose of Treatment K</arm_group_label>
      <other_name>hPTH(1-34)</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>EBP22</intervention_name>
      <description>Oral tablets</description>
      <arm_group_label>Treatment I EBP22 1.5 mg</arm_group_label>
      <arm_group_label>Treatment J EBP22 1.5 mg</arm_group_label>
      <arm_group_label>Treatment K oral EBP formulation determined based on IA results</arm_group_label>
      <arm_group_label>Treatment L BID of oral EBP formulation determined based on IA results</arm_group_label>
      <arm_group_label>Treatment N single dose of Treatment K</arm_group_label>
      <other_name>hPTH(1-34)</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>EBP11-M</intervention_name>
      <description>Oral tablets</description>
      <arm_group_label>Treatment H EBP11-M 1.5 mg</arm_group_label>
      <arm_group_label>Treatment K oral EBP formulation determined based on IA results</arm_group_label>
      <arm_group_label>Treatment L BID of oral EBP formulation determined based on IA results</arm_group_label>
      <arm_group_label>Treatment N single dose of Treatment K</arm_group_label>
      <other_name>hPTH(1-34)</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Healthy male subjects, 18 - 35 years of age, inclusive, at screening.&#xD;
  &#xD;
            2. Continuous nonsmoker who has not used nicotine containing products (including&#xD;
               e-cigarettes, vapors, etc.) for at least 12 months prior to first dosing and&#xD;
               throughout the study, based on subject self-reporting.&#xD;
  &#xD;
            3. Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at screening.&#xD;
  &#xD;
            4. Medically healthy with no clinically significant medical condition, physical&#xD;
               examination, laboratory profiles, vital signs, orthostatic vital sign measurements, or&#xD;
               ECGs, as deemed by the PI or designee to be relevant to the study and does not pose an&#xD;
               additional risk to the subject by their participation in the study.&#xD;
  &#xD;
            5. Understands the study procedures described in the Informed Consent Form (ICF), be&#xD;
               willing and able to comply with the protocol, and provides written consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. History or current condition of mental instability or cognitive impairment that, in&#xD;
               the opinion of the investigator, could compromise the validity of informed consent,&#xD;
               compromise the safety of the participant, or lead to nonadherence with the study&#xD;
               protocol or inability to conduct the study procedures.&#xD;
  &#xD;
            2. Active gastrointestinal inflammatory disorder, gastrointestinal motility disorders,&#xD;
               and chronic gastritis, including but not limited to: ulcerative colitis, Crohn's&#xD;
               disease, irritable bowel syndrome, short bowel syndrome, celiac disease,&#xD;
               gastroparesis, that may affect drug bioavailability.&#xD;
  &#xD;
            3. Any conditions or factors that, in the judgment of the PI or designee, somehow may&#xD;
               impact gastrointestinal absorption, distribution or metabolism of parathyroid hormone&#xD;
               analogues, or known to potentiate or predispose to undesired effects.&#xD;
  &#xD;
            4. History of significant gastrointestinal, liver or kidney disease, or gastrointestinal&#xD;
               surgery (including bariatric surgery, or any other interventional procedures with&#xD;
               stomach and intestinal tract) that may affect either drug bioavailability, or&#xD;
               hPTH(1-34) or SNAC metabolism.&#xD;
  &#xD;
            5. History or presence of alcohol or drug abuse or positive urine drug or blood alcohol&#xD;
               results at screening.&#xD;
  &#xD;
            6. Known allergies or sensitivities to components of the Study Medication (e.g. soy) or&#xD;
               known hypersensitivity to PTH or hPTH(1-34).&#xD;
  &#xD;
            7. History or presence of clinically significant:&#xD;
  &#xD;
                 -  Urolithiasis;&#xD;
  &#xD;
                 -  Angina at Screening, in the opinion of the PI;&#xD;
  &#xD;
                 -  Hypocalcemia or hypercalcemia at screening;&#xD;
  &#xD;
                 -  Personal or family history of congenital long QT syndrome or known family history&#xD;
                    of sudden death.&#xD;
  &#xD;
            8. Subjects with ECG findings deemed abnormal with clinical significance by the PI or&#xD;
               designee at screening for the following:&#xD;
  &#xD;
                 -  QTcF interval &gt; 470 msec;&#xD;
  &#xD;
                 -  PR &gt; 220 msec;&#xD;
  &#xD;
                 -  QRS &gt; 120 msec.&#xD;
  &#xD;
            9. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B&#xD;
               surface antigen (HBsAg) or hepatitis C virus (HCV).&#xD;
  &#xD;
           10. Seated blood pressure is less than 90 systolic or 40 diastolic mmHg or greater than&#xD;
               140 systolic or 90 diastolic mmHg at screening;&#xD;
  &#xD;
           11. Orthostatic vital sign results with a decrease in systolic &gt; 20 mmHg or decrease in&#xD;
               diastolic &gt; 10 mm Hg, and/or increase in heart rate of &gt; 20 beats per minute at&#xD;
               screening or Day 1 check-in.&#xD;
  &#xD;
           12. Seated heart rate is lower than 50 bpm or higher than 99 bpm at screening (when&#xD;
               clinically significant as determined by PI).&#xD;
  &#xD;
           13. Estimated creatinine clearance &lt; 80 mL/min at screening&#xD;
  &#xD;
           14. Unable to refrain from or anticipates the use of:&#xD;
  &#xD;
                 -  Any drug, including prescription and nonprescription medications, herbal&#xD;
                    remedies, or vitamin supplements that should be taken on the treatment visit day&#xD;
                    before the dosing of Study Medication and 2 hours after the dosing of Study&#xD;
                    Medication.&#xD;
  &#xD;
                 -  H2 blocker or PPI or antacid (including prescription and nonprescription) three&#xD;
                    days before the dosing of the Study Medication and 2 hours after the dosing of&#xD;
                    Study Medication.&#xD;
  &#xD;
           15. Donation of blood or significant blood loss within 56 days prior to first dosing.&#xD;
  &#xD;
           16. Hemoglobin levels below 13 g/dL at screening or at in screening test done during the&#xD;
               study.&#xD;
  &#xD;
           17. Plasma donation within 7 days prior to first dosing.&#xD;
  &#xD;
           18. Participation in another interventional clinical study within 30 days prior to&#xD;
               screening visit.&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <gender_based>Yes</gender_based>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>35 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Arthur C Santora, MD</last_name>
      <role>Study Director</role>
      <affiliation>Entera Bio Chief Medical Officer</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Clinical Research Center Hadassah Ein Kerem Medical Center</name>
        <address>
          <city>Jerusalem</city>
          <zip>91120,</zip>
          <country>Israel</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Yosef Caraco, MD</last_name>
        <phone>02-677-8584</phone>
        <email>caraco@hadassah.org.il</email>
      </contact>
      <investigator>
        <last_name>Yosef Caraco, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Israel</country>
    </location_countries>
    <verification_date>June 2023</verification_date>
    <study_first_submitted>June 8, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Hypoparathyroidism</keyword>
    <keyword>PTH(1-34)</keyword>
    <keyword>Parathyroid Hormone</keyword>
    <keyword>Teriparatide</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Hypoparathyroidism</mesh_term>
    </condition_browse>
    <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>
  
  
text: 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/NCT05965167
  org study id: ENT-11-2023
  nct id: NCT05965167
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this study is to characterize and compare the pharmacokinetics of hPTH(1 34)
        after treatment with a modified oral formulation (EBP11, EBP11-M, and EBP22) versus two dose
        levels of Entera Bio's extensively studied oral EBP05 1.5 mg and 2.5 mg as well as the
        commercial Forteo 0.02 mg subcutaneous injection.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Assessment of the pharmacokinetic profile of plasma hPTH(1-34) after single or twice daily oral administration for treatment regimen as listed under Arms and Interventions at 5, 10, 15, 20, 40, 50, 60, 75, 90, 105, 120, 180, 240, 360 min. post dose
  time frame: 6 hours
  description: Pharmacokinetic parameter - plasma hPTH(1-34) in pg/mL
  measure: Calculation of plasma levels of hPTH(1-34) AUC0-t for each treatment regimen
  time frame: 6 hours
  description: Pharmacokinetic parameter - total drug exposure at different time points up to 360 min. post dose
  measure: Calculation of plasma levels of hPTH(1-34) AUC0-inf for each treatment regimen
  time frame: 6-14 hours
  description: Pharmacokinetic parameter - total drug exposure in pg/mL over time from 0 extrapolated to infinity
  measure: Calculation of plasma levels of hPTH(1-34) AUC%extrap for each treatment regimen
  time frame: 6-14 hours
  description: Pharmacokinetic parameter - Percent of AUC0-inf extrapolated to confirm reliability
  measure: Calculation of plasma levels of hPTH(1-34) Cmax for each treatment regimen
  time frame: 6-14 hours
  description: Pharmacokinetic parameter - hPTH (1-34) maximal concentration in pg/mL (Cmax)
  measure: Calculation of plasma levels of hPTH(1-34) Tmax for each treatment regimen
  time frame: 6-14 hours
  description: Pharmacokinetic parameter - time in minutes to reach max. concentration of hPTH(1-34)
  measure: Calculation of plasma levels of hPTH(1-34) Kel for each treatment regimen
  time frame: 6 hours
  description: Pharmacokinetic parameter - elimination rate constant in pg/mL, fraction of drug eliminated per time-point up to 360 min. post dose
  measure: Calculation of plasma levels of hPTH(1-34) t½ for each treatment regimen
  time frame: 6-14 hours
  description: Pharmacokinetic parameter - terminal elimination half life of hPTH(1-34) in minutes
  measure: Calculation of plasma levels of hPTH(1-34) Tlast for each treatment regimen
  time frame: 6-14 hours
  description: Pharmacokinetic parameter - time of the last measurable concentration of hPTH(1-34) in minutes
  measure: Assessment of inter-subject variability of hPTH(1-34) for each treatment regimen
  time frame: 6-14 hours
  description: Pharmacokinetic parameter - Coefficient of Variance (CV%) of hPTH (1-34)
  measure: Calculation of dose proportionality for hPTH(1-34) for relevant treatment regimen
  time frame: 6 hours
  description: Pharmacokinetic parameter
  measure: Assessment of the duration of exposure to hPTH(1-34) in minutes
  time frame: 6 hours
  description: Pharmacokinetic parameter - up to 360 min. post dose
  measure: Vital Signs - body temperature (Celsius)
  time frame: 6 hours
  description: Safety parameter (group mean at each time point up to 360 min. post dose)
  measure: Vital Signs - respiratory rate (breaths per minute)
  time frame: 6 hours
  description: Safety parameter (group mean at each time point up to 360 min. post dose)
  measure: Vital Signs - blood pressure (systolic/diastolic mmHg)
  time frame: 6 hours
  description: Safety parameter (group mean at each time point up to 360 min. post dose)
  measure: Vital Signs - heart rate (beats per minute)
  time frame: 6 hours
  description: Safety parameter (group mean at each time point up to 360 min. post dose)
  measure: Incidence of Treatment-Emergent Adverse Events as assessed by the Principle Investigator
  time frame: 6-14 hours
  description: Safety parameter - AEs observed over duration of study participation
  measure: Incidence of Serious Adverse Events (SAEs) as assessed by the Principle Investigator
  time frame: 6-14 hours
  description: Safety parameter - SAEs observed over duration of study participation
  measure: Measurement of plasma soybean trypsin inhibitor, Kunitz type (SBTI) levels (EBP05 only)
  time frame: 6 hours
  description: Pharmacokinetic parameter in ng/mL
  measure: Measurement of plasma salcaprozate sodium (SNAC) levels (EBP05 only)
  time frame: 6 hours
  description: Pharmacokinetic parameter in μg/mL
  measure: Measurement of serum calcium (albumin-corrected total calcium) for all treatment regimen
  time frame: 6 hours
  description: Pharmacodynamic parameter in mg/dL at 120, 240, 360 min post dose
  measure: Measurement of serum phosphate for all treatment regimen
  time frame: 6 hours
  description: Pharmacodynamic parameter in mg/dL at 120, 240, 360 min post dose
  measure: Measurement of serum intact hPTH(1-84) for all treatment regimen
  time frame: 6 hours
  description: Pharmacodynamic parameter in pg/mL at 120, 240, 360 min post dose
  measure: Measurement of serum 1,25-(OH)2D for all treatment regimen (optional)
  time frame: 6 hours
  description: Pharmacodynamic parameter in ng/mL at 120, 240, 360 min post dose
  arm group label: Treatment A EBP05 2.5 mg
  arm group type: Experimental
  description: Single dose of oral EBP05 2.5 mg
  arm group label: Treatment B EBP05 1.5 mg
  arm group type: Experimental
  description: Single dose of oral EBP05 1.5 mg
  arm group label: Treatment C Forteo 20 mg
  arm group type: Experimental
  description: Single SC injection of Forteo 0.02 mg
  arm group label: Treatment D EBP11 1.5 mg
  arm group type: Experimental
  description: Single dose of oral EBP11 1.5 mg
  arm group label: Treatment E EBP11 BID (dose determined after IA)
  arm group type: Experimental
  description: Based on PK data from 1st Interim Analysis BID administration of oral EBP11. The selected BID dose to be administered will be either 1.5, 2.0 or 2.5 mg.
  arm group label: Treatment F EBP11 BID (dose determined after IA)
  arm group type: Experimental
  description: BID administration of oral EBP11 tablets. The selected EBP11 dose will be either 1.5, 2.0 or 2.5 mg based on hPTH(1-34) PK data from the 1st and 2nd Interim Analyses.
  arm group label: Treatment G EBP11 1.5 mg
  arm group type: Experimental
  description: Single dose of oral EBP11 1.5 mg
  arm group label: Treatment H EBP11-M 1.5 mg
  arm group type: Experimental
  description: Single dose of oral EBP11-M 1.5 mg
  arm group label: Treatment I EBP22 1.5 mg
  arm group type: Experimental
  description: Single dose of oral EBP22 1.5 mg
  arm group label: Treatment J EBP22 1.5 mg
  arm group type: Experimental
  description: Single dose of oral EBP22 1.5 mg
  arm group label: Treatment K oral EBP formulation determined based on IA results
  arm group type: Experimental
  description: Single dose of oral 1.5 mg of the selected oral formulation (EBP11, EBP11-M, or EBP22) based on the results of all Cohort 1 and 2 Interim Analyses
  arm group label: Treatment L BID of oral EBP formulation determined based on IA results
  arm group type: Experimental
  description: BID dose of oral 1.5 mg of the selected oral formulation (EBP11, EBP11-M, or EBP22) based on the results of all Cohort 1 and 2 Interim Analyses
  arm group label: Treatment M BID of EBP05 2.5 mg
  arm group type: Experimental
  description: BID dose of oral EBP05 2.5 mg
  arm group label: Treatment N single dose of Treatment K
  arm group type: Experimental
  description: Single dose of Treatment K
  intervention type: Drug
  intervention name: EBP05
  description: Oral tablets
  arm group label: Treatment A EBP05 2.5 mg
  arm group label: Treatment B EBP05 1.5 mg
  arm group label: Treatment M BID of EBP05 2.5 mg
  other name: hPTH(1-34)
  intervention type: Drug
  intervention name: Forteo 20 mg
  description: Subcutaneous injection
  arm group label: Treatment C Forteo 20 mg
  other name: hPTH(1-34)
  intervention type: Drug
  intervention name: EBP11
  description: Oral tablets
  arm group label: Treatment D EBP11 1.5 mg
  arm group label: Treatment E EBP11 BID (dose determined after IA)
  arm group label: Treatment F EBP11 BID (dose determined after IA)
  arm group label: Treatment G EBP11 1.5 mg
  arm group label: Treatment K oral EBP formulation determined based on IA results
  arm group label: Treatment L BID of oral EBP formulation determined based on IA results
  arm group label: Treatment N single dose of Treatment K
  other name: hPTH(1-34)
  intervention type: Drug
  intervention name: EBP22
  description: Oral tablets
  arm group label: Treatment I EBP22 1.5 mg
  arm group label: Treatment J EBP22 1.5 mg
  arm group label: Treatment K oral EBP formulation determined based on IA results
  arm group label: Treatment L BID of oral EBP formulation determined based on IA results
  arm group label: Treatment N single dose of Treatment K
  other name: hPTH(1-34)
  intervention type: Drug
  intervention name: EBP11-M
  description: Oral tablets
  arm group label: Treatment H EBP11-M 1.5 mg
  arm group label: Treatment K oral EBP formulation determined based on IA results
  arm group label: Treatment L BID of oral EBP formulation determined based on IA results
  arm group label: Treatment N single dose of Treatment K
  other name: hPTH(1-34)
  criteria: 
  gender: Male
  gender based: Yes
  minimum age: 18 Years
  maximum age: 35 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Arthur C Santora, MD
  role: Study Director
  affiliation: Entera Bio Chief Medical Officer
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: Israel
  responsible party type: Sponsor
  mesh term: Hypoparathyroidism
  mesh term: Teriparatide