<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/NCT03781947</url>
  </required_header>
  <id_info>
    <org_study_id>ANT-1111-P01</org_study_id>
    <nct_id>NCT03781947</nct_id>
  </id_info>
  <brief_title>A Study of Parenterally-administered Teverelix TFA in Healthy Male Volunteers</brief_title>
  <official_title>A Phase I, Open-label, Single Centre Study Investigating the PK, Safety and PD of a Single Dose of Teverelix TFA, a GnRH Antagonist, Via s.c. or i.m. Route of Administration in Healthy Male Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Antev Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Antev 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>
      A Phase I, open-label, single centre study investigating the pharmacokinetics, safety and&#xD;
      pharmacodynamics of a single dose of teverelix TFA, a gonadotrophin releasing hormone&#xD;
      antagonist, via subcutaneous or intramuscular route of administration in healthy male&#xD;
      volunteers&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of the study is:&#xD;
&#xD;
      • To characterise the pharmacokinetic (PK) profile of teverelix following single dose,&#xD;
      subcutaneous (s.c.) and intramuscular (i.m.) administration of teverelix TFA in healthy male&#xD;
      subjects&#xD;
&#xD;
      The secondary objectives of the study are:&#xD;
&#xD;
        -  To assess the safety and tolerability of teverelix TFA after single s.c. and i.m.&#xD;
           injections in healthy male subjects&#xD;
&#xD;
        -  To evaluate pharmacodynamics (PD) effects of teverelix following single dose, s.c. and&#xD;
           i.m. administration of teverelix TFA in healthy male subjects&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 19, 2018</start_date>
  <completion_date type="Actual">March 16, 2020</completion_date>
  <primary_completion_date type="Actual">March 16, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This Phase I clinical study is an open-label, parallel-design, single-centre study to investigate the PK, safety and PD following subcutaneous and intramuscular administration of single doses of teverelix TFA in healthy male subjects.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-t</measure>
    <time_frame>12 weeks</time_frame>
    <description>Area under the concentration time-curve from time zero up to the last measurable concentration at time point t Area under the concentration time-curve from time zero up to the last measurable concentration at time point t Area under the concentration time-curve from time zero up to the last measurable concentration at time point t</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-t1</measure>
    <time_frame>12 weeks</time_frame>
    <description>Area under the concentration time-curve from time zero up to concentration at time point t1 after which the concentrations start to rise again towards a second peak, t1 will be determined after review of the concentration-time profiles (immediate release component of total observed AUC)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUCt1-t</measure>
    <time_frame>12 weeks</time_frame>
    <description>Area under the concentration time-curve from time point t1 up to time point t (slow release component of total observed AUC)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-∞</measure>
    <time_frame>12 weeks</time_frame>
    <description>Area under the concentration time-curve from time zero up to infinity (∞)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax</measure>
    <time_frame>12 weeks</time_frame>
    <description>Maximum observed concentration after administration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax,0-t1</measure>
    <time_frame>12 weeks</time_frame>
    <description>Maximum observed concentration after administration from zero up to time point t1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax,t1-t</measure>
    <time_frame>12 weeks</time_frame>
    <description>Maximum observed concentration after administration from time point t1 up to time point t</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax</measure>
    <time_frame>12 weeks</time_frame>
    <description>Time to reach Cmax after dosing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax,0-t1</measure>
    <time_frame>12 weeks</time_frame>
    <description>Time to reach Cmax,0-t1 after dosing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax,t1-t</measure>
    <time_frame>12 weeks</time_frame>
    <description>Time to reach Cmax,t1-t after dosing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>λz</measure>
    <time_frame>12 weeks</time_frame>
    <description>Apparent terminal rate constant</description>
  </primary_outcome>
  <primary_outcome>
    <measure>t½</measure>
    <time_frame>12 weeks</time_frame>
    <description>Apparent terminal plasma half-life</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Systemic tolerability - Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>12 weeks</time_frame>
    <description>Systemic tolerability assessed by incidence of treatment emergent AEs (TEAEs)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local tolerability - Standardised Injection Site Reaction Scoring System (4-point) plus photography</measure>
    <time_frame>12 weeks</time_frame>
    <description>The injections sites will be assessed (score 0 = none; 1 = mild; 2 = moderate; 3 = severe and undesirable) for signs of erythema, swelling, bruising, itching, pain and other signs of local reactions. Subjects will be monitored for duration of symptoms, sequelae and impact on activities of daily living (ADL). Photographs of all injection sites will be taken at all study visits post-administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac assessments</measure>
    <time_frame>12 weeks</time_frame>
    <description>The following 12-lead ECG parameters will be assessed: PR interval, QRS interval, RR interval, QT interval and QTc interval (QTcF)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>24 hour Holter monitoring</measure>
    <time_frame>Day -1 to Day 1</time_frame>
    <description>Triplicate 10 second 12-lead ECGs will be extracted at time points prior to PK sampling times (Day 1) and matched timepoints (Day -1) in order to facilitate concentration-QTc effect modelling</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Testosterone (total) levels</measure>
    <time_frame>12 weeks</time_frame>
    <description>Individual data listings of hormone level results will be presented for each subject</description>
  </other_outcome>
  <other_outcome>
    <measure>Luteinising Hormone (LH) levels</measure>
    <time_frame>12 weeks</time_frame>
    <description>Individual data listings of hormone level results will be presented for each subject</description>
  </other_outcome>
  <other_outcome>
    <measure>Follicle Stimulating Hormone (FSH) levels</measure>
    <time_frame>12 weeks</time_frame>
    <description>Individual data listings of hormone level results will be presented for each subject</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>90 mg s.c.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single s.c. injection of 90 mg teverelix TFA administered on Day 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>60 mg s.c.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single s.c. injection of 60 mg teverelix TFA administered on Day 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>90 mg i.m.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single i.m. injection of 90 mg teverelix TFA administered on Day 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>120 mg s.c.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single s.c. injection of 120 mg teverelix TFA administered on Day 1</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>teverelix TFA</intervention_name>
    <description>A single s.c. or i.m. injection of teverelix TFA administered on Day 1</description>
    <arm_group_label>120 mg s.c.</arm_group_label>
    <arm_group_label>60 mg s.c.</arm_group_label>
    <arm_group_label>90 mg i.m.</arm_group_label>
    <arm_group_label>90 mg s.c.</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provide voluntarily agreement to participate in this study and sign an Independent&#xD;
             Ethics Committee (IEC)-approved informed consent prior to performing any of the&#xD;
             screening procedures.&#xD;
&#xD;
          2. Males of any ethnic origin, between 40 to 70 years of age (inclusive) at the screening&#xD;
             visit.&#xD;
&#xD;
          3. Healthy, determined by pre-study medical evaluation (medical history, vital signs,&#xD;
             physical examination, standard 12-lead ECG and clinical laboratory evaluations).&#xD;
&#xD;
             If a vital sign or ECG assessment is outside of the reference range at the screening&#xD;
             visit or admission, the assessment may be repeated once to rule out any error.&#xD;
&#xD;
          4. Body mass index (BMI) between 20.0 and 34.9 kg/m2 (inclusive) at the screening visit&#xD;
             and on admission.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Clinically relevant history of cardiovascular, respiratory, hepatic, renal,&#xD;
             pancreatic, gastrointestinal, metabolic, endocrine, neurological, dermatological,&#xD;
             immunological, psychiatric or other diseases/disorders as determined by the Principal&#xD;
             Investigator or designee, or evidence of such diseases/disorders during the screening&#xD;
             period.&#xD;
&#xD;
          2. Any disorder or clinically relevant surgical history that would interfere with the&#xD;
             absorption, distribution, metabolism or excretion of the study drug.&#xD;
&#xD;
          3. History of proneness to orthostatic dysregulation, fainting or blackouts.&#xD;
&#xD;
          4. History or physical evidence of chronic or clinically relevant acute infection.&#xD;
&#xD;
          5. Screening total testosterone &lt;3.0 ng/mL (&lt;10.4 nmol/L).&#xD;
&#xD;
          6. History of anaphylactoid reactions or hypersensitivity to teverelix or GnRH&#xD;
             antagonists or any of the excipients of the products tested.&#xD;
&#xD;
          7. History of clinically relevant allergies or idiosyncrasies to medication or food.&#xD;
&#xD;
          8. History of regular alcohol consumption exceeding 21 units per week within 2 years of&#xD;
             study entry.&#xD;
&#xD;
          9. History of illicit drug abuse within 2 years of study entry.&#xD;
&#xD;
         10. Any ECG abnormality of clinical relevance; ECG QT interval corrected for heart rate&#xD;
             using Fridericia's correction (QTcF) &gt; 450 ms at the screening visit.&#xD;
&#xD;
         11. Any clinically relevant findings in the laboratory tests, as judged by the Principal&#xD;
             Investigator, at the screening visit and on admission; alanine aminotransferase (ALT)&#xD;
             &gt; 1.5 x the upper limit of normal (ULN) and/or aspartate aminotransferase (AST) &gt; 1.5&#xD;
             x ULN and/or total bilirubin &gt; 1.0 x ULN, as confirmed by subsequent repeat&#xD;
             assessment, at the screening visit and on admission. If a laboratory assessment is&#xD;
             outside of the reference range at the screening visit or admission, the assessment may&#xD;
             be repeated once to rule out laboratory error.&#xD;
&#xD;
         12. An estimated glomerular filtration rate (eGFR) &lt; 90 mL/min, based on creatinine&#xD;
             clearance calculation by the Cockcroft Gault formula and normalised to an average&#xD;
             surface area of 1.73m2, at the screening visit.&#xD;
&#xD;
         13. Positive results in any of the tests for hepatitis B surface antigen (HBsAg), total&#xD;
             hepatitis B core antibody (HBcAb), hepatitis C antibody (anti-HCV) or human&#xD;
             immunodeficiency virus (HIV) antibodies, at the screening visit.&#xD;
&#xD;
         14. Positive urine test for ethanol and/or drugs of abuse at the screening visit or&#xD;
             admission.&#xD;
&#xD;
         15. Use of prescription, non-prescription and over-the-counter (OTC) medications&#xD;
             (including vitamins or herbal remedies) within 2 weeks prior to dosing is prohibited.&#xD;
&#xD;
         16. Receiving an investigational product in a clinical trial within 3 months prior to the&#xD;
             screening visit.&#xD;
&#xD;
         17. Donation of blood (&gt; 500 mL) or blood products within 2 months (56 days) prior to the&#xD;
             screening visit.&#xD;
&#xD;
         18. Unwilling to avoid consumption of coffee and caffeine-containing products within 48&#xD;
             hours prior to admission until discharge from the study centre, as well as from 48&#xD;
             hours before ambulatory visits.&#xD;
&#xD;
         19. Unwilling to avoid use of alcohol or alcohol-containing foods, medications or&#xD;
             beverages, within 48 hours prior to admission until discharge from the study centre,&#xD;
             as well as from 48 hours before ambulatory visits.&#xD;
&#xD;
         20. Unwilling to abstain from vigorous exercise from 72 hours prior to admission until&#xD;
             discharge from the study centre, as well as from 72 hours before ambulatory visits.&#xD;
&#xD;
         21. Unable to understand the protocol requirements, instructions and study related&#xD;
             restrictions, the nature, scope and possible consequences of the clinical study.&#xD;
&#xD;
         22. Subject is unlikely to comply with the protocol requirements, instructions and study&#xD;
             related restrictions; e.g., uncooperative attitude, inability to return for follow-up&#xD;
             visits and improbability of completing the clinical study.&#xD;
&#xD;
         23. Subject has any concurrent condition that, in the opinion of the Principal&#xD;
             Investigator, would make the subject unsuitable for participation in the clinical&#xD;
             study.&#xD;
&#xD;
         24. Subject is an employee or the close relative of an employee of the Sponsor or the&#xD;
             clinical research organisation (CRO) involved in the clinical study.&#xD;
&#xD;
         25. Vulnerable subjects defined as individuals whose willingness to volunteer in a&#xD;
             clinical study may be unduly influenced by the expectation, whether justified or not,&#xD;
             of benefits associated with participation, or of a retaliatory response from senior&#xD;
             members of a hierarchy in case of refusal to participate (e.g., persons in detention,&#xD;
             minors and those incapable of giving consent).&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Healthy male volunteers</gender_description>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pablo Forte Soto, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Parexel</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PAREXEL International Early Phase Clinical Unit (EPCU)</name>
      <address>
        <city>London</city>
        <state>Middlesex</state>
        <zip>HA1 3UJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>March 16, 2020</last_update_submitted>
  <last_update_submitted_qc>March 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 17, 2020</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>Antarelix</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03781947
org study id: ANT-1111-P01
nct id: NCT03781947
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A Phase I, open-label, single centre study investigating the pharmacokinetics, safety and
      pharmacodynamics of a single dose of teverelix TFA, a gonadotrophin releasing hormone
      antagonist, via subcutaneous or intramuscular route of administration in healthy male
      volunteers
The primary objective of the study is:

      • To characterise the pharmacokinetic (PK) profile of teverelix following single dose,
      subcutaneous (s.c.) and intramuscular (i.m.) administration of teverelix TFA in healthy male
      subjects

      The secondary objectives of the study are:

        -  To assess the safety and tolerability of teverelix TFA after single s.c. and i.m.
           injections in healthy male subjects

        -  To evaluate pharmacodynamics (PD) effects of teverelix following single dose, s.c. and
           i.m. administration of teverelix TFA in healthy male subjects
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: This Phase I clinical study is an open-label, parallel-design, single-centre study to investigate the PK, safety and PD following subcutaneous and intramuscular administration of single doses of teverelix TFA in healthy male subjects.
primary purpose: Basic Science
masking: None (Open Label)
measure: AUC0-t
time frame: 12 weeks
description: Area under the concentration time-curve from time zero up to the last measurable concentration at time point t Area under the concentration time-curve from time zero up to the last measurable concentration at time point t Area under the concentration time-curve from time zero up to the last measurable concentration at time point t
measure: AUC0-t1
time frame: 12 weeks
description: Area under the concentration time-curve from time zero up to concentration at time point t1 after which the concentrations start to rise again towards a second peak, t1 will be determined after review of the concentration-time profiles (immediate release component of total observed AUC)
measure: AUCt1-t
time frame: 12 weeks
description: Area under the concentration time-curve from time point t1 up to time point t (slow release component of total observed AUC)
measure: AUC0-∞
time frame: 12 weeks
description: Area under the concentration time-curve from time zero up to infinity (∞)
measure: Cmax
time frame: 12 weeks
description: Maximum observed concentration after administration
measure: Cmax,0-t1
time frame: 12 weeks
description: Maximum observed concentration after administration from zero up to time point t1
measure: Cmax,t1-t
time frame: 12 weeks
description: Maximum observed concentration after administration from time point t1 up to time point t
measure: Tmax
time frame: 12 weeks
description: Time to reach Cmax after dosing
measure: Tmax,0-t1
time frame: 12 weeks
description: Time to reach Cmax,0-t1 after dosing
measure: Tmax,t1-t
time frame: 12 weeks
description: Time to reach Cmax,t1-t after dosing
measure: λz
time frame: 12 weeks
description: Apparent terminal rate constant
measure: t½
time frame: 12 weeks
description: Apparent terminal plasma half-life
measure: Systemic tolerability - Incidence of Treatment-Emergent Adverse Events
time frame: 12 weeks
description: Systemic tolerability assessed by incidence of treatment emergent AEs (TEAEs)
measure: Local tolerability - Standardised Injection Site Reaction Scoring System (4-point) plus photography
time frame: 12 weeks
description: The injections sites will be assessed (score 0 = none; 1 = mild; 2 = moderate; 3 = severe and undesirable) for signs of erythema, swelling, bruising, itching, pain and other signs of local reactions. Subjects will be monitored for duration of symptoms, sequelae and impact on activities of daily living (ADL). Photographs of all injection sites will be taken at all study visits post-administration
measure: Cardiac assessments
time frame: 12 weeks
description: The following 12-lead ECG parameters will be assessed: PR interval, QRS interval, RR interval, QT interval and QTc interval (QTcF)
measure: 24 hour Holter monitoring
time frame: Day -1 to Day 1
description: Triplicate 10 second 12-lead ECGs will be extracted at time points prior to PK sampling times (Day 1) and matched timepoints (Day -1) in order to facilitate concentration-QTc effect modelling
measure: Testosterone (total) levels
time frame: 12 weeks
description: Individual data listings of hormone level results will be presented for each subject
measure: Luteinising Hormone (LH) levels
time frame: 12 weeks
description: Individual data listings of hormone level results will be presented for each subject
measure: Follicle Stimulating Hormone (FSH) levels
time frame: 12 weeks
description: Individual data listings of hormone level results will be presented for each subject
arm group label: 90 mg s.c.
arm group type: Experimental
description: A single s.c. injection of 90 mg teverelix TFA administered on Day 1
arm group label: 60 mg s.c.
arm group type: Experimental
description: A single s.c. injection of 60 mg teverelix TFA administered on Day 1
arm group label: 90 mg i.m.
arm group type: Experimental
description: A single i.m. injection of 90 mg teverelix TFA administered on Day 1
arm group label: 120 mg s.c.
arm group type: Experimental
description: A single s.c. injection of 120 mg teverelix TFA administered on Day 1
intervention type: Drug
intervention name: teverelix TFA
description: A single s.c. or i.m. injection of teverelix TFA administered on Day 1
arm group label: 120 mg s.c.
arm group label: 60 mg s.c.
arm group label: 90 mg i.m.
arm group label: 90 mg s.c.
criteria: 
gender: Male
gender based: Yes
gender description: Healthy male volunteers
minimum age: 40 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pablo Forte Soto, MD
role: Principal Investigator
affiliation: Parexel
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Antarelix
sharing ipd: No