<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/NCT03774459</url>
  </required_header>
  <id_info>
    <org_study_id>ANAVEX2-73-PDD-001</org_study_id>
    <nct_id>NCT03774459</nct_id>
  </id_info>
  <brief_title>ANAVEX2-73 Study in Parkinson's Disease Dementia</brief_title>
  <official_title>A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of ANAVEX2-73 for Cognitive Impairment in Patients With Parkinson's Disease With Dementia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Anavex Life Sciences Corp.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Anavex Germany GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Anavex Life Sciences Corp.</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 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety,&#xD;
      Tolerability, and Efficacy of ANAVEX2-73 for Cognitive Impairment in Patients with&#xD;
      Parkinson's Disease with Dementia (PDD)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group,&#xD;
      three-arm, 14-week study in PD patients with dementia. The study includes a 2 week Screening&#xD;
      / Baseline Observation Period and a 14-week Treatment Period (including a 2 week Titration&#xD;
      Period), and a 2-week Safety Follow-Up Period&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 9, 2018</start_date>
  <completion_date type="Actual">September 30, 2020</completion_date>
  <primary_completion_date type="Actual">September 30, 2020</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>Cognitive Drug Research (CDR) Computerized Assessment System Continuity of Attention</measure>
    <time_frame>14 weeks</time_frame>
    <description>Change from Baseline to End of Treatment in Continuity of Attention as measured by Cognitive Drug Research (CDR) Computerized Assessment System Continuity of Attention test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>14 weeks</time_frame>
    <description>Assess the safety and tolerability of ANAVEX2-73 compared to placebo</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>MDS-UPDRS Part III Total Score (Motor Scores)</measure>
    <time_frame>14 weeks</time_frame>
    <description>Change from baseline to End of Treatment as measured by MDS-UPDRS Part III Total Score (Motor Scores)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SDS-CL-25</measure>
    <time_frame>14 weeks</time_frame>
    <description>Incidence of sleep disorders symptoms (SDS-CL-25)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">132</enrollment>
  <condition>Parkinsons Disease With Dementia</condition>
  <arm_group>
    <arm_group_label>High dose ANAVEX2-73</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High dose ANAVEX2-73</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mid dose ANAVEX2-73</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mid dose ANAVEX2-73</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo oral capsule</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo oral capsule</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High dose ANAVEX2-73</intervention_name>
    <description>Active oral capsule</description>
    <arm_group_label>High dose ANAVEX2-73</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mid dose ANAVEX2-73</intervention_name>
    <description>Active oral capsule</description>
    <arm_group_label>Mid dose ANAVEX2-73</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>Placebo oral capsule</description>
    <arm_group_label>Placebo oral capsule</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of idiopathic Parkinson's disease (PD) consistent with the UK Parkinson's&#xD;
             Disease Society Brain Bank diagnostic criteria.&#xD;
&#xD;
          -  Diagnosis of probable PD dementia (PDD) according to the Movement Disorder Society&#xD;
             Task Force clinical diagnostic criteria.&#xD;
&#xD;
          -  Montreal Cognitive Assessment (MoCA) score of 13 to 23, inclusive, at Screening.&#xD;
&#xD;
          -  Male or female and aged ≥ 50 years.&#xD;
&#xD;
          -  Caregivers and subjects (or legal representative) must understand and have signed&#xD;
             approved informed consent.&#xD;
&#xD;
          -  Caregivers and subjects (or legal representative) must be able to understand study&#xD;
             requirements and be willing to follow instructions.&#xD;
&#xD;
          -  Stable regimen of anti-Parkinson's disease medications (including levodopa, dopamine&#xD;
             agonists, MAO-B inhibitors, or the COMT inhibitor entacapone), which has been stable&#xD;
             for at least 4 weeks prior to Baseline.&#xD;
&#xD;
          -  Treatment with cholinesterase inhibitor (rivastigmine, donepezil and galantamine&#xD;
             (Exelon®, Aricept®, or Reminyl®) will be permitted, provided the dose has been stable&#xD;
             for a minimum of 8 weeks prior to randomization.&#xD;
&#xD;
          -  Subjects with history of depression on antidepressant medications will be allowed if&#xD;
             depression is controlled and they have been on a stable daily dose of the&#xD;
             antidepressant for ≥8 weeks before Baseline.&#xD;
&#xD;
          -  Contraception:&#xD;
&#xD;
               -  Women of childbearing potential must use an acceptable method of contraception&#xD;
                  starting 4 weeks prior to study drug administration and for a minimum of 4 weeks&#xD;
                  after study completion. Otherwise, women must be postmenopausal (at least one&#xD;
                  year absence of vaginal bleeding or spotting) as confirmed by FSH greater than or&#xD;
                  equal to 40 mIU/mL or 40 IU/L or be surgically sterile.&#xD;
&#xD;
               -  Men with a potentially fertile partner must have had a vasectomy or be willing to&#xD;
                  use an acceptable method of contraception for the duration of the study and for 3&#xD;
                  months after study drug discontinuation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of any significant neurologic or psychiatric disorder other than PD that can&#xD;
             contribute to cognitive impairment.&#xD;
&#xD;
          -  Any other condition or clinically significant abnormal findings like severe&#xD;
             co-morbidities e.g. history of stroke, poor kidney or liver function on the physical&#xD;
             or neurological examination, medical and psychiatric history, at screening or at&#xD;
             baseline that, in the opinion of the Investigator, would make the subject unsuitable&#xD;
             for the study.&#xD;
&#xD;
          -  Potential symptomatic causes of cognitive impairment including but not limited to&#xD;
&#xD;
               1. abnormal thyroid function test at screening (TSH)&#xD;
&#xD;
               2. abnormal B12 level at screening&#xD;
&#xD;
               3. MRI findings (by history) pointing to a potential symptomatic cause of cognitive&#xD;
                  dysfunction, including significant vascular changes, or communicating&#xD;
                  hydrocephalus.&#xD;
&#xD;
          -  Treatment with memantine or amantadine. If appropriate the drugs can be discontinued&#xD;
             for a minimum of 4 weeks prior to randomization.&#xD;
&#xD;
          -  Use of over the counter (OTC) or prescription medication for sleep on 2 or more&#xD;
             occasions per week (less than that is allowed).&#xD;
&#xD;
          -  History of depression as measured by Beck Depression Inventory score &gt;17 at screening.&#xD;
&#xD;
          -  Treatment with any other investigational drug or device within 4 weeks prior to&#xD;
             screening.&#xD;
&#xD;
          -  Smoking &gt; 1 pack of cigarettes per day (as assessed for the 4 weeks prior to&#xD;
             screening).&#xD;
&#xD;
          -  Women who are pregnant or lactating.&#xD;
&#xD;
          -  Known allergy or sensitivity to ANAVEX2-73 or any of its components.&#xD;
&#xD;
          -  Suicidal ideation on the Columbia Suicide Severity Rating Scale (C-SSRS) of type 4 or&#xD;
             type 5, or any suicidal behavior, in the past 6 months. Type 4 indicates active&#xD;
             suicidal ideation with some intent to act, without a specific plan. Type 5 indicates&#xD;
             active suicidal ideation with a specific plan and intent.&#xD;
&#xD;
          -  Use of centrally acting anticholinergic drugs during the 4 weeks before randomization.&#xD;
&#xD;
          -  Medications used for overactive bladder will be allowed provided that the regimen has&#xD;
             been stable 4 weeks prior to randomization.&#xD;
&#xD;
          -  Treatment with any dopamine receptor blocking medications with the exception of low&#xD;
             dose quetiapine (≤50 mg/day). Pimavanserin (≤34 mg/day) will be allowed.&#xD;
&#xD;
          -  History of neurosurgical intervention (e.g., deep brain stimulation) for PD.&#xD;
&#xD;
          -  Unpredictable motor fluctuations that would interfere with administering cognitive&#xD;
             assessments in the ON state.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>KaRa MINDS</name>
      <address>
        <city>Macquarie Park</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hammond Health</name>
      <address>
        <city>Malvern</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Cruces Bilbao</name>
      <address>
        <city>Barakaldo</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de la Santa Creu i Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Mutua Terrasa</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Burgos</name>
      <address>
        <city>Burgos</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Puerta del Mar</name>
      <address>
        <city>Cadiz</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Henares</name>
      <address>
        <city>Coslada</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Elche</name>
      <address>
        <city>Elche</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Arquitecto Marcide</name>
      <address>
        <city>Ferrol</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Santa Caterina</name>
      <address>
        <city>Girona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Ruber Internacional</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clínica Universidad de Navarra (CUN) - Sede Madrid- Servicio de Neurología -</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico San Carlos</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de La Princesa</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañón</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Infanta Leónor</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Puerta de Hierro</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital HM Puerta del Sur</name>
      <address>
        <city>Móstoles</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Central de Asturias (HUCA)</name>
      <address>
        <city>Oviedo</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clínica Universidad de Navarra (CUN)</name>
      <address>
        <city>Pamplona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Santiago de Compostela</name>
      <address>
        <city>Santiago de Compostela</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Spain</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>December 8, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 13, 2018</study_first_posted>
  <last_update_submitted>October 19, 2020</last_update_submitted>
  <last_update_submitted_qc>October 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2020</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>Parkinson Disease</mesh_term>
    <mesh_term>Dementia</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/NCT03774459
org study id: ANAVEX2-73-PDD-001
nct id: NCT03774459
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety,
      Tolerability, and Efficacy of ANAVEX2-73 for Cognitive Impairment in Patients with
      Parkinson's Disease with Dementia (PDD)
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group,
      three-arm, 14-week study in PD patients with dementia. The study includes a 2 week Screening
      / Baseline Observation Period and a 14-week Treatment Period (including a 2 week Titration
      Period), and a 2-week Safety Follow-Up Period
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Cognitive Drug Research (CDR) Computerized Assessment System Continuity of Attention
time frame: 14 weeks
description: Change from Baseline to End of Treatment in Continuity of Attention as measured by Cognitive Drug Research (CDR) Computerized Assessment System Continuity of Attention test
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: 14 weeks
description: Assess the safety and tolerability of ANAVEX2-73 compared to placebo
measure: MDS-UPDRS Part III Total Score (Motor Scores)
time frame: 14 weeks
description: Change from baseline to End of Treatment as measured by MDS-UPDRS Part III Total Score (Motor Scores)
measure: SDS-CL-25
time frame: 14 weeks
description: Incidence of sleep disorders symptoms (SDS-CL-25)
arm group label: High dose ANAVEX2-73
arm group type: Experimental
description: High dose ANAVEX2-73
arm group label: Mid dose ANAVEX2-73
arm group type: Experimental
description: Mid dose ANAVEX2-73
arm group label: Placebo oral capsule
arm group type: Placebo Comparator
description: Placebo oral capsule
intervention type: Drug
intervention name: High dose ANAVEX2-73
description: Active oral capsule
arm group label: High dose ANAVEX2-73
intervention type: Drug
intervention name: Mid dose ANAVEX2-73
description: Active oral capsule
arm group label: Mid dose ANAVEX2-73
intervention type: Drug
intervention name: Placebo oral capsule
description: Placebo oral capsule
arm group label: Placebo oral capsule
criteria: 
gender: All
minimum age: 50 Years
maximum age: 85 Years
healthy volunteers: No
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country: Australia
country: Spain
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Dementia