<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/NCT03244228</url>
  </required_header>
  <id_info>
    <org_study_id>HTL0016878-101</org_study_id>
    <secondary_id>2017-001385-26</secondary_id>
    <secondary_id>16-028</secondary_id>
    <nct_id>NCT03244228</nct_id>
  </id_info>
  <brief_title>A Two Part Study to Assess Safety, PK, PD, and Food Effect of Oral HTL0016878</brief_title>
  <official_title>A Two-part, Randomised, Double-blind, Placebo-controlled Single and Multiple Ascending Dose Study to Assess Safety, Pharmacokinetics and Pharmacodynamics of Oral HTL0016878 in Healthy Younger Adult and Elderly Subjects With a Randomised, Open-label, Crossover Arm to Assess the Effect of Food on Bioavailability of Oral HTL0016878.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Heptares Therapeutics Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Allergan</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Heptares Therapeutics Limited</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase 1, first in human, two-part, single centre, placebo-controlled, single and multiple&#xD;
      ascending dose trial in healthy younger and elderly adult subjects, with an open-label,&#xD;
      randomised, crossover arms to assess the effect of food on bioavailability.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a first in human single and multiple ascending dose study with the objective to&#xD;
      evaluate safety, tolerability, PK, PD, and food effect of HTL0016878 in healthy younger and&#xD;
      elderly subjects. Part 1 will assess single doses of HTL0016878 and Part 2 will assess&#xD;
      multiple doses of HTL0016878. Part 1 will be divided into 3 sub-parts: Part 1a will assess&#xD;
      single ascending doses (SAD) of HTL0016878 in younger adult subjects, Part 1b will evaluate&#xD;
      the effect of food on bioavailability of HTL0016878 and part 1c will investigate the effect&#xD;
      of age on the PK of HTL0016878. Part 1c will only proceed after review of safety,&#xD;
      tolerability and PK data from part 1a. Part 2 will be divided into 2 sub-parts to assess&#xD;
      multiple ascending doses (MAD) of HTL0016878 in younger adult (part 2a) and elderly adult&#xD;
      (part 2b) subjects. Part 2 will only proceed after review of safety, tolerability and PK data&#xD;
      from Parts 1a, b and c.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 25, 2017</start_date>
  <completion_date type="Actual">September 23, 2019</completion_date>
  <primary_completion_date type="Actual">September 23, 2019</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Treatment emergent adverse events (TEAEs)</measure>
    <time_frame>Baseline up to 14 days post dose</time_frame>
    <description>Safety and Tolerability</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physical examinations</measure>
    <time_frame>Baseline up to 14 days post dose</time_frame>
    <description>Safety and Tolerability</description>
  </primary_outcome>
  <primary_outcome>
    <measure>vital signs (Heart Rate and Blood pressure)</measure>
    <time_frame>Baseline up to 14 days post dose</time_frame>
    <description>Safety and Tolerability</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Laboratory safety assessment</measure>
    <time_frame>Baseline up to 14 days post dose</time_frame>
    <description>Safety and Tolerability</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ECG</measure>
    <time_frame>Baseline up to 14 days post dose</time_frame>
    <description>Safety and Tolerability</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Columbia- suicide severity rating scale (C-SSRS)</measure>
    <time_frame>Baseline up to 14 days post dose</time_frame>
    <description>Safety and Tolerability</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma concentration (Cmax) of HTL0016878</measure>
    <time_frame>Baseline up to 14 days post dose</time_frame>
    <description>Pharmacokinetics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum plasma concentration (Tmax) of HTL0016878</measure>
    <time_frame>Baseline up to 14 days post dose</time_frame>
    <description>Pharmacokinetics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve of HTL0016878</measure>
    <time_frame>Baseline up to 14 days post dose</time_frame>
    <description>Pharmacokinetics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life (t1/2) of HTL0016878</measure>
    <time_frame>Baseline up to 14 days post dose</time_frame>
    <description>Pharmacokinetics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount excreted in urine (Ae) of HTL0016878</measure>
    <time_frame>Baseline up to 14 days post dose</time_frame>
    <description>Pharmacokinetics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of dose eliminated unchanged on urine (fe/F) of HTL0016878</measure>
    <time_frame>Baseline up to 14 days post dose</time_frame>
    <description>Pharmacokinetics</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Part 1a SAD HTL0016878/Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Part 1a, single ascending doses of HLT0016878 or matching placebo will be administered to groups of 12 subject each (9 active, 3 placebo). Each subject will have up to four treatment sessions separated by an appropriate wash-out. Healthy, young, male subjects.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1b single dose HTL0016878</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Part 1b, a single dose of HTL0016878 will be administered to 6 subjects on two occasions: once in the fasted and once the fed state. This will be open-label. Healthy, young, male or female subjects.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1c single dose HTL0016878</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Part 1c, a single dose of HTL0016878 will be administered to up to 6 (optional up to 12) healthy elderly subjects This will be open-label. Healthy, elderly, male subjects.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2a MAD HTL0016878/Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Part 2a, multiple doses of HTL0016878 will be administered to up to 5 cohorts (N=8, 6 active, 2 placebo) during one study session of 7 days. Healthy, young, male or female subjects.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2b MAD HTL0016878/Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Part 2b, multiple doses of HTL0016878 will be administered to up to 3 cohorts of healthy, elderly subjects (N=8, 6 active, 2 placebo) during one study session of 7 days. Healthy, young, male or female subjects.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HTL0016878</intervention_name>
    <description>Oral solution</description>
    <arm_group_label>Part 1a SAD HTL0016878/Placebo</arm_group_label>
    <arm_group_label>Part 1b single dose HTL0016878</arm_group_label>
    <arm_group_label>Part 1c single dose HTL0016878</arm_group_label>
    <arm_group_label>Part 2a MAD HTL0016878/Placebo</arm_group_label>
    <arm_group_label>Part 2b MAD HTL0016878/Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo - Concentrate</intervention_name>
    <description>Matching placebo</description>
    <arm_group_label>Part 1a SAD HTL0016878/Placebo</arm_group_label>
    <arm_group_label>Part 2a MAD HTL0016878/Placebo</arm_group_label>
    <arm_group_label>Part 2b MAD HTL0016878/Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Normotensive 18-55 year old (Parts 1a, 1b and 2a only) or 65+ year old (Parts 1c and&#xD;
             2b) male (all parts) or female (parts 1b, 2a and 2b only) volunteers with a body mass&#xD;
             index 18-32kg/m².&#xD;
&#xD;
          -  Healthy on the basis of a clinical history, physical examination, electrocardiogram&#xD;
             (ECG), vital signs, heart rate (part 1a only), exercise history (part 1a only), and&#xD;
             laboratory tests of blood and urine.&#xD;
&#xD;
          -  Willingness to comply with requirements or the trial, including contraception&#xD;
             requirements.&#xD;
&#xD;
          -  Able to give fully informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Positive tests for hepatitis B &amp; C, HIV&#xD;
&#xD;
          -  severe adverse reaction to any drug&#xD;
&#xD;
          -  sensitivity to trial medication&#xD;
&#xD;
          -  drug or alcohol abuse&#xD;
&#xD;
          -  smoking&#xD;
&#xD;
          -  use of medication that inhibits CYP2D6 within previous 21 days or other prescribed and&#xD;
             over-the-counter medication and herbal remedies within previous 21 days before dosing&#xD;
             (with the exception of acetaminophen, contraceptive medications and hormone&#xD;
             replacement therapy), unless the principal investigator (PI) considers that it would&#xD;
             not interfere with trial&#xD;
&#xD;
          -  participation in other clinical trials of unlicensed medicines in the previous 3&#xD;
             months, or regularly take part in more than 4 studies a year&#xD;
&#xD;
          -  loss of more than 500 mL blood in the previous 3 months&#xD;
&#xD;
          -  vital signs, QTcF interval or laboratory values outside the acceptable range&#xD;
&#xD;
          -  poor metabolizers of CYP2D6 (apart from one optional cohort in Part 1a, which may&#xD;
             enrol poor metabolizers only)&#xD;
&#xD;
          -  clinically relevant abnormal findings at the screening assessment&#xD;
&#xD;
          -  acute or chronic illness&#xD;
&#xD;
          -  history of epilepsy or seizures&#xD;
&#xD;
          -  clinically relevant abnormal medical history or concurrent medical condition&#xD;
&#xD;
          -  disease associated with cognitive impairment and/or psychosis&#xD;
&#xD;
          -  recent history of suicidal thoughts or ideation, or insomnia&#xD;
&#xD;
          -  excessive use of caffeine containing beverages, exceeding 8 cups of coffee or&#xD;
             equivalent/day and the inability to refrain from the use of caffeine containing&#xD;
             beverages whilst on the ward&#xD;
&#xD;
          -  consumption of cranberry, pomegranate, star fruit, grapefruit, pomelos, exotic citrus&#xD;
             fruits or Seville oranges (including marmalade and juices made from these fruits)&#xD;
             within 3 days before admission; possibility that volunteer will not cooperate&#xD;
&#xD;
          -  pre-menopausal females who are pregnant or lactating, or who are sexually active and&#xD;
             not using a reliable method of contraception&#xD;
&#xD;
          -  Objection by the GP.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hammersmith Medicines Research</name>
      <address>
        <city>London</city>
        <state>Hammersmith</state>
        <zip>NW10 7EW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>November 27, 2019</last_update_submitted>
  <last_update_submitted_qc>November 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>First in human</keyword>
  <keyword>Multiple ascending dose</keyword>
  <keyword>Single ascending dose</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/NCT03244228
org study id: HTL0016878-101
secondary id: 2017-001385-26
secondary id: 16-028
nct id: NCT03244228
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Phase 1, first in human, two-part, single centre, placebo-controlled, single and multiple
      ascending dose trial in healthy younger and elderly adult subjects, with an open-label,
      randomised, crossover arms to assess the effect of food on bioavailability.
This is a first in human single and multiple ascending dose study with the objective to
      evaluate safety, tolerability, PK, PD, and food effect of HTL0016878 in healthy younger and
      elderly subjects. Part 1 will assess single doses of HTL0016878 and Part 2 will assess
      multiple doses of HTL0016878. Part 1 will be divided into 3 sub-parts: Part 1a will assess
      single ascending doses (SAD) of HTL0016878 in younger adult subjects, Part 1b will evaluate
      the effect of food on bioavailability of HTL0016878 and part 1c will investigate the effect
      of age on the PK of HTL0016878. Part 1c will only proceed after review of safety,
      tolerability and PK data from part 1a. Part 2 will be divided into 2 sub-parts to assess
      multiple ascending doses (MAD) of HTL0016878 in younger adult (part 2a) and elderly adult
      (part 2b) subjects. Part 2 will only proceed after review of safety, tolerability and PK data
      from Parts 1a, b and c.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double blind
measure: Treatment emergent adverse events (TEAEs)
time frame: Baseline up to 14 days post dose
description: Safety and Tolerability
measure: Physical examinations
time frame: Baseline up to 14 days post dose
description: Safety and Tolerability
measure: vital signs (Heart Rate and Blood pressure)
time frame: Baseline up to 14 days post dose
description: Safety and Tolerability
measure: Laboratory safety assessment
time frame: Baseline up to 14 days post dose
description: Safety and Tolerability
measure: ECG
time frame: Baseline up to 14 days post dose
description: Safety and Tolerability
measure: Columbia- suicide severity rating scale (C-SSRS)
time frame: Baseline up to 14 days post dose
description: Safety and Tolerability
measure: Maximum plasma concentration (Cmax) of HTL0016878
time frame: Baseline up to 14 days post dose
description: Pharmacokinetics
measure: Time to Maximum plasma concentration (Tmax) of HTL0016878
time frame: Baseline up to 14 days post dose
description: Pharmacokinetics
measure: Area under the curve of HTL0016878
time frame: Baseline up to 14 days post dose
description: Pharmacokinetics
measure: Half-life (t1/2) of HTL0016878
time frame: Baseline up to 14 days post dose
description: Pharmacokinetics
measure: Amount excreted in urine (Ae) of HTL0016878
time frame: Baseline up to 14 days post dose
description: Pharmacokinetics
measure: Fraction of dose eliminated unchanged on urine (fe/F) of HTL0016878
time frame: Baseline up to 14 days post dose
description: Pharmacokinetics
arm group label: Part 1a SAD HTL0016878/Placebo
arm group type: Experimental
description: In Part 1a, single ascending doses of HLT0016878 or matching placebo will be administered to groups of 12 subject each (9 active, 3 placebo). Each subject will have up to four treatment sessions separated by an appropriate wash-out. Healthy, young, male subjects.
arm group label: Part 1b single dose HTL0016878
arm group type: Experimental
description: In Part 1b, a single dose of HTL0016878 will be administered to 6 subjects on two occasions: once in the fasted and once the fed state. This will be open-label. Healthy, young, male or female subjects.
arm group label: Part 1c single dose HTL0016878
arm group type: Experimental
description: In Part 1c, a single dose of HTL0016878 will be administered to up to 6 (optional up to 12) healthy elderly subjects This will be open-label. Healthy, elderly, male subjects.
arm group label: Part 2a MAD HTL0016878/Placebo
arm group type: Experimental
description: In Part 2a, multiple doses of HTL0016878 will be administered to up to 5 cohorts (N=8, 6 active, 2 placebo) during one study session of 7 days. Healthy, young, male or female subjects.
arm group label: Part 2b MAD HTL0016878/Placebo
arm group type: Experimental
description: In Part 2b, multiple doses of HTL0016878 will be administered to up to 3 cohorts of healthy, elderly subjects (N=8, 6 active, 2 placebo) during one study session of 7 days. Healthy, young, male or female subjects.
intervention type: Drug
intervention name: HTL0016878
description: Oral solution
arm group label: Part 1a SAD HTL0016878/Placebo
arm group label: Part 1b single dose HTL0016878
arm group label: Part 1c single dose HTL0016878
arm group label: Part 2a MAD HTL0016878/Placebo
arm group label: Part 2b MAD HTL0016878/Placebo
intervention type: Drug
intervention name: Placebo - Concentrate
description: Matching placebo
arm group label: Part 1a SAD HTL0016878/Placebo
arm group label: Part 2a MAD HTL0016878/Placebo
arm group label: Part 2b MAD HTL0016878/Placebo
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
responsible party type: Sponsor
sharing ipd: No