<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/NCT04462263</url>
  </required_header>
  <id_info>
    <org_study_id>HTL0014242-103</org_study_id>
    <secondary_id>2020-000602-28</secondary_id>
    <secondary_id>247490</secondary_id>
    <nct_id>NCT04462263</nct_id>
  </id_info>
  <brief_title>Study to Investigate the Receptor Occupancy of HTL0014242 Using [18F] FPEB in Healthy Male Subjects</brief_title>
  <official_title>An Open-label, Single Centre, Single Oral Dose Study to Investigate the Receptor Occupancy of HTL0014242 Using [18F] FPEB in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Heptares Therapeutics Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Heptares Therapeutics Limited</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 Study in Healthy Volunteers to Investigate How a New Drug for the Treatment of Parkinson's&#xD;
      Disease, Dystonia and Amyotrophic Lateral Sclerosis Binds to Receptor Sites in the Brain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, single dose, adaptive study of orally adminstered HTL0014242 in up to&#xD;
      10 healthy male subjects. The primary objective is to investigate the&#xD;
      pharmacokinetic-receptor occupancy relationship of single oral doses of HTL0014242 in healthy&#xD;
      subjects. The secondary objectives are to assess the plasma pharmacokinetics (PK), safety and&#xD;
      tolerability of single oral doses of HTL0014242 in healthy subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 29, 2020</start_date>
  <completion_date type="Actual">June 23, 2021</completion_date>
  <primary_completion_date type="Actual">June 23, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Receptor Occupancy Endpoint</measure>
    <time_frame>Day 1 post-dose timepoint</time_frame>
    <description>The regional brain Receptor Occupancy profile of HTL0014242, measured by Positron Emission Tomography (PET) imaging with[18F]FPEB</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Receptor Occupancy Endpoint</measure>
    <time_frame>Day 2 post-dose timepoint</time_frame>
    <description>The regional brain Receptor Occupancy profile of HTL0014242, measured by Positron Emission Tomography (PET) imaging with[18F]FPEB</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax: Maximum plasma concentration</measure>
    <time_frame>Baseline up to 14(+3) days post dose</time_frame>
    <description>Pharmacokinetics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma-concentration curve</measure>
    <time_frame>Baseline up to 14(+3) days post dose</time_frame>
    <description>Pharmacokinetics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum plasma concentration (Tmax) of HTL0014242</measure>
    <time_frame>Baseline up to 14(+3) days post dose</time_frame>
    <description>Pharmacokinetics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life (t1/2) of HTL0014242</measure>
    <time_frame>Baseline up to 14(+3) days post dose</time_frame>
    <description>Pharmacokinetics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent total plasma clearance (CL/F)</measure>
    <time_frame>Baseline up to 14(+3) days post dose</time_frame>
    <description>Pharmacokinetics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment Emergent Adverse Events (TEAEs)</measure>
    <time_frame>Baseline up to 14(+3) days post dose</time_frame>
    <description>Safety and Tolerability</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Single Dose HTL0014242</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The study consists of up to 5 dosing groups, with 2 to 3 subjects per dosing group. Each subject will receive a single oral dose of HTL0014242 in the form of solid suspension capsules (1, 5, 10, and 30mg) as required. HTL0014242 will be administered in up to 5 single dose groups, with 120mg administered in the first dosing group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HTL0014242</intervention_name>
    <description>Solid suspension capsule</description>
    <arm_group_label>Single Dose HTL0014242</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male, aged between 23 and 55 years inclusive, with body mass index between&#xD;
             18.5 and 32 kg/m2.&#xD;
&#xD;
          -  Healthy on the basis of a clinical history, physical examination, electrocardiogram&#xD;
             (ECG), vital signs and laboratory tests of blood and urine.&#xD;
&#xD;
          -  Able to give fully informed consent and has suitable veins for cannulation and&#xD;
             arterial access in both wrists&#xD;
&#xD;
          -  Resting BP and heart rate within normal ranges after 5 mins rest.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Past, current or family history of mental, behavioural or neurodevelopmental disorder.&#xD;
&#xD;
          -  Clinically significant history or evidence of cardiovascular, respiratory, hepatic,&#xD;
             renal, gastrointestinal, endocrine, neurological, immunological, pyschiatric&#xD;
             disorders, metabolic, allergic, dermatological, haematological, pulmonary or&#xD;
             respiratory disorder.&#xD;
&#xD;
          -  History of significant hypersensitivity, intolerance or allergy to any drug compound,&#xD;
             food or other substance, unless approved by Investigator.&#xD;
&#xD;
          -  Active neoplastic disease or history of any neoplastic disease within 5 years of&#xD;
             screening.&#xD;
&#xD;
          -  Active infection (e.g sepsis, pneumonia, abscess) or serious infection (e.g resulting&#xD;
             in hospitalisation or requiring parenteral antibiotic treatment) within 90 days prior&#xD;
             to dosing.&#xD;
&#xD;
          -  History of stomach or intestinal surgery or resection.&#xD;
&#xD;
          -  Any of following at screening or pre-dose: QT internal heart rate correction; QRS&#xD;
             duration &gt;120ms; PR interval &gt; 220ms; QTc measurements/data difficult or&#xD;
             uninterpreable; history of additional risk factors for torsades de pointe.&#xD;
&#xD;
          -  drug or alcohol abuse in last 2 years.&#xD;
&#xD;
          -  Alcohol consumption is &gt; 14 units per week&#xD;
&#xD;
          -  Positive Urine alcohol or drug tests&#xD;
&#xD;
          -  Positive HIV, Hep B, Hep C test&#xD;
&#xD;
          -  Aspartate aminotransferase, Alanine aminotransferase, Gamma glutamyl transferase,&#xD;
             Alkaline phosphatase or total bilirubin above normal upper limits&#xD;
&#xD;
          -  Participation in other clinical trials of unlicensed medicines in the previous 3&#xD;
             months, or 7 half-lives of the medicine (whichever is longer)&#xD;
&#xD;
          -  Previously dosed with HTL0014242.&#xD;
&#xD;
          -  Intention to use or using medications that interfere with drug absorption, metabolism&#xD;
             or elimination processes incl St John's Wort, 30 days prior to dosing.&#xD;
&#xD;
          -  Use of ketamine, amphetamines or MDMA with 9o days prior to dosing&#xD;
&#xD;
          -  Use or intend to use any prescription or non-prescription medications within 14 days&#xD;
             or 5 half-lives of medication, prior to dosing. Investigator and study team to&#xD;
             determine implications on safety or study procedures, on a case-by-case basis.&#xD;
&#xD;
          -  Received live attenuated vaccination within 6 weeks prior to Screening, or intends to&#xD;
             receive vaccination during the study.&#xD;
&#xD;
          -  Smoker or user of tobacco- or nicotine-containing products.&#xD;
&#xD;
          -  Receipt of blood products within 2 months prior to dosing. Donation of blood /&#xD;
             comparable blood loss 3 months prior to dosing.&#xD;
&#xD;
          -  Abnormal Allen's circulation test result. Evaluation of arterial access indicates risk&#xD;
             of occlusion or insufficient supply. Evaluation of venous access indicates&#xD;
             difficulties in obtaining venous blood.&#xD;
&#xD;
          -  Subject unable or unwilling to abstain from alcohol or caffeine-containing foods and&#xD;
             beverages. Significant consumption of any foods or beverages containing CYP1A2&#xD;
             inducers with 2 weeks prior to Admission (Investigator opinion).&#xD;
&#xD;
          -  Significant consumption of any foods or beverages containing Seville-type oranges,&#xD;
             grapefruit, or poppy seeds within 7 days prior to baseline PET and admission&#xD;
             (Investigator opinion).&#xD;
&#xD;
          -  Subject, in opinion of Investigator should not participate in this study. Reply from&#xD;
             GP, for this specific study probing psychiatric history must be received before&#xD;
             dosing.&#xD;
&#xD;
          -  Participation in research study or other radiation exposure (e.g workplace) which in&#xD;
             conjunction with this study will exceed ionisation radiation exposure over 10mSv&#xD;
             within 12 months prior to the Screening visit.&#xD;
&#xD;
          -  Contraindication for MRI, assessed by standard pre-MRI questionnaire, that preclude&#xD;
             subject undergoing MRI scans.&#xD;
&#xD;
          -  Subject suffers from claustrophobia (incapable of undergoing MRI or PET scan) or&#xD;
             needle phobia.&#xD;
&#xD;
          -  Subject has abnormal findings per structural MRI scan at screening.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>23 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Parexel Early Phase Clinical Unit</name>
      <address>
        <city>Harrow</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>July 2021</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>July 6, 2021</last_update_submitted>
  <last_update_submitted_qc>July 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Single dose</keyword>
  <keyword>Open-label</keyword>
  <keyword>Oral</keyword>
  <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/NCT04462263
org study id: HTL0014242-103
secondary id: 2020-000602-28
secondary id: 247490
nct id: NCT04462263
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A Study in Healthy Volunteers to Investigate How a New Drug for the Treatment of Parkinson's
      Disease, Dystonia and Amyotrophic Lateral Sclerosis Binds to Receptor Sites in the Brain.
This is an open-label, single dose, adaptive study of orally adminstered HTL0014242 in up to
      10 healthy male subjects. The primary objective is to investigate the
      pharmacokinetic-receptor occupancy relationship of single oral doses of HTL0014242 in healthy
      subjects. The secondary objectives are to assess the plasma pharmacokinetics (PK), safety and
      tolerability of single oral doses of HTL0014242 in healthy subjects.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Receptor Occupancy Endpoint
time frame: Day 1 post-dose timepoint
description: The regional brain Receptor Occupancy profile of HTL0014242, measured by Positron Emission Tomography (PET) imaging with[18F]FPEB
measure: Receptor Occupancy Endpoint
time frame: Day 2 post-dose timepoint
description: The regional brain Receptor Occupancy profile of HTL0014242, measured by Positron Emission Tomography (PET) imaging with[18F]FPEB
measure: Cmax: Maximum plasma concentration
time frame: Baseline up to 14(+3) days post dose
description: Pharmacokinetics
measure: Area under the plasma-concentration curve
time frame: Baseline up to 14(+3) days post dose
description: Pharmacokinetics
measure: Time to Maximum plasma concentration (Tmax) of HTL0014242
time frame: Baseline up to 14(+3) days post dose
description: Pharmacokinetics
measure: Half-life (t1/2) of HTL0014242
time frame: Baseline up to 14(+3) days post dose
description: Pharmacokinetics
measure: Apparent total plasma clearance (CL/F)
time frame: Baseline up to 14(+3) days post dose
description: Pharmacokinetics
measure: Incidence of Treatment Emergent Adverse Events (TEAEs)
time frame: Baseline up to 14(+3) days post dose
description: Safety and Tolerability
arm group label: Single Dose HTL0014242
arm group type: Experimental
description: The study consists of up to 5 dosing groups, with 2 to 3 subjects per dosing group. Each subject will receive a single oral dose of HTL0014242 in the form of solid suspension capsules (1, 5, 10, and 30mg) as required. HTL0014242 will be administered in up to 5 single dose groups, with 120mg administered in the first dosing group.
intervention type: Drug
intervention name: HTL0014242
description: Solid suspension capsule
arm group label: Single Dose HTL0014242
criteria: 
gender: Male
gender based: Yes
minimum age: 23 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
responsible party type: Sponsor
sharing ipd: No