<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/NCT01661673</url>
  </required_header>
  <id_info>
    <org_study_id>EVP-0962-002</org_study_id>
    <nct_id>NCT01661673</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacokinetics of EVP-0962 and Effects of EVP-0962 on Cerebral Spinal Fluid Amyloid Concentrations in Healthy Subjects and in Subjects With Mild Cognitive Impairment or Early Alzheimer's Disease</brief_title>
  <official_title>Safety, Tolerability, Pharmacokinetics, and Effects of EVP-0962 on Cerebral Spinal Fluid Amyloid Concentrations in Healthy Subjects and in Subjects With Mild Cognitive Impairment or Early Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>FORUM Pharmaceuticals Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Parexel</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>FORUM Pharmaceuticals Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is being conducted to determine the safety, tolerability, pharmacokinetics, and&#xD;
      effects of EVP-0962 on cerebral spinal fluid Amyloid concentrations in healthy subjects and&#xD;
      in subjects with mild cognitive impairment or early Alzheimer's disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, sequential escalating repeat daily dose study conducted&#xD;
      in two parts. The first part is being conducted in healthy subjects and will evaluate safety,&#xD;
      tolerability, and pharmacokinetics and pharmacodynamics of escalating EVP-0962 doses (10, 50&#xD;
      100 and 200 mg) or matching placebo following once-daily administration for 14 days. The&#xD;
      second part will evaluate the safety, tolerability and pharmacokinetics and pharmacodynamics&#xD;
      of EVP-0962 following once-daily administration for 14 days in patients with mild cognitive&#xD;
      impairment or early Alzheimer's disease at the dose level selected based on the available&#xD;
      safety, pharmacokinetics and pharmacodynamics observations in the first part.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <primary_completion_date type="Actual">October 2013</primary_completion_date>
  <phase>Phase 2</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>
  </study_design_info>
  <primary_outcome>
    <measure>The number of adverse experiences reported by subjects and/or observed by investigator and repeated clinical evaluations of physical examinations, vital signs, 12-lead ECG (electrocardiogram), and lab tests (hematology, chemistry, urinalysis)</measure>
    <time_frame>Screening (Day-45 to Day -1) through Day 23 (end of study visit)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To measure the rate of synthesis of Amyloid Beta in cerebral spinal fluid of healthy subjects</measure>
    <time_frame>0-36 hours post dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To measure the concentration of Amyloid Beta in cerebral spinal fluid</measure>
    <time_frame>0-36 hours post dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>To measure the rate of synthesis of Amyloid Beta and steady-state levels in the cerebral spinal fluid in MCI or early Alzheimer's disease patients</measure>
    <time_frame>0-36 hours post dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine single-and repeat-dose EVP-0962 pharmacokinetics in cerebral spinal fluid and plasma</measure>
    <time_frame>0-36 hours post dose</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">52</enrollment>
  <condition>Mild Cognitive Impairment</condition>
  <condition>Alzheimer's Disease</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 mg EVP-0962 Orally administered once daily for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 mg EVP-0962 Orally administered once daily for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100 mg EVP-0962 Orally administered once daily for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>200 mg EVP-0962 Orally administered once daily for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 5</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo orally administered for 14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EVP-0962</intervention_name>
    <description>Arms: 1,2,3,4</description>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_label>Arm 2</arm_group_label>
    <arm_group_label>Arm 3</arm_group_label>
    <arm_group_label>Arm 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Arm 5</description>
    <arm_group_label>Arm 5</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Part 1: Male and female subjects between the ages of 45 to 65 (inclusive) in good&#xD;
             health with a BMI of 18-32 kg/m2 and negative urine drug screen of abuse test.&#xD;
&#xD;
          -  Part 2: Male and female subjects between the ages of 45 to 85 (inclusive), MRI/CT&#xD;
             scans compatible with diagnosis of MCI or early AD, meets the classification of MCI&#xD;
             due to AD as defined by the National Institute on Aging-Alzheimer's Association, and a&#xD;
             BMI of 18-32 kg/m2(inclusive). Subjects must meet the following Cognitive criteria:&#xD;
             Subject Memory Complaint, cognitive impairment in one or more areas, CDR-SB score less&#xD;
             than or equal 1.0, MMSE greater than 24, and no impairment in social or occupational&#xD;
             functioning.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of seizure disorder, symptomatic orthostatic hypotension, QTc values greater&#xD;
             than 450 ms, positive drug screening tests&#xD;
&#xD;
          -  Pregnancy, nursing, (or if fertile female) not willing to utilize birth control&#xD;
             measures during study&#xD;
&#xD;
          -  C-SSRS suicidal ideation score of 4 or 5&#xD;
&#xD;
          -  Unwilling to abstain from vigorous exercise&#xD;
&#xD;
          -  Concurrent disease other than MCI or early AD that is attributing to patient's&#xD;
             cognitive impairment.&#xD;
&#xD;
          -  Lumbar spine X-rays show anatomic contraindications to lumbar puncture&#xD;
&#xD;
          -  History of spinal surgery or chronic low back pain&#xD;
&#xD;
          -  History of migraine headaches&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Glendale Adventist Medical Center</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2014</verification_date>
  <study_first_submitted>August 3, 2012</study_first_submitted>
  <study_first_submitted_qc>August 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <last_update_submitted>January 10, 2014</last_update_submitted>
  <last_update_submitted_qc>January 10, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 13, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01661673
org study id: EVP-0962-002
nct id: NCT01661673
lead sponsor: 
collaborator: 
has dmc: No
This study is being conducted to determine the safety, tolerability, pharmacokinetics, and
      effects of EVP-0962 on cerebral spinal fluid Amyloid concentrations in healthy subjects and
      in subjects with mild cognitive impairment or early Alzheimer's disease.
This is a randomized, double-blind, sequential escalating repeat daily dose study conducted
      in two parts. The first part is being conducted in healthy subjects and will evaluate safety,
      tolerability, and pharmacokinetics and pharmacodynamics of escalating EVP-0962 doses (10, 50
      100 and 200 mg) or matching placebo following once-daily administration for 14 days. The
      second part will evaluate the safety, tolerability and pharmacokinetics and pharmacodynamics
      of EVP-0962 following once-daily administration for 14 days in patients with mild cognitive
      impairment or early Alzheimer's disease at the dose level selected based on the available
      safety, pharmacokinetics and pharmacodynamics observations in the first part.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The number of adverse experiences reported by subjects and/or observed by investigator and repeated clinical evaluations of physical examinations, vital signs, 12-lead ECG (electrocardiogram), and lab tests (hematology, chemistry, urinalysis)
time frame: Screening (Day-45 to Day -1) through Day 23 (end of study visit)
measure: To measure the rate of synthesis of Amyloid Beta in cerebral spinal fluid of healthy subjects
time frame: 0-36 hours post dose
measure: To measure the concentration of Amyloid Beta in cerebral spinal fluid
time frame: 0-36 hours post dose
measure: To measure the rate of synthesis of Amyloid Beta and steady-state levels in the cerebral spinal fluid in MCI or early Alzheimer's disease patients
time frame: 0-36 hours post dose
measure: To determine single-and repeat-dose EVP-0962 pharmacokinetics in cerebral spinal fluid and plasma
time frame: 0-36 hours post dose
arm group label: Arm 1
arm group type: Experimental
description: 10 mg EVP-0962 Orally administered once daily for 14 days
arm group label: Arm 2
arm group type: Experimental
description: 50 mg EVP-0962 Orally administered once daily for 14 days
arm group label: Arm 3
arm group type: Experimental
description: 100 mg EVP-0962 Orally administered once daily for 14 days
arm group label: Arm 4
arm group type: Experimental
description: 200 mg EVP-0962 Orally administered once daily for 14 days
arm group label: Arm 5
arm group type: Placebo Comparator
description: Placebo orally administered for 14 days
intervention type: Drug
intervention name: EVP-0962
description: Arms: 1,2,3,4
arm group label: Arm 1
arm group label: Arm 2
arm group label: Arm 3
arm group label: Arm 4
intervention type: Drug
intervention name: Placebo
description: Arm 5
arm group label: Arm 5
criteria: 
gender: All
minimum age: 45 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Cognitive Dysfunction