<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/NCT02221947</url>
  </required_header>
  <id_info>
    <org_study_id>NTRP101-201</org_study_id>
    <nct_id>NCT02221947</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Preliminary Safety, Efficacy, PK and PD of Bryostatin 1 in Patients With Alzheimer's Disease</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Preliminary Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Bryostatin 1 in Patients With Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neurotrope Bioscience, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Blanchette Rockefeller Neurosciences Insitute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Neurotrope Bioscience, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is being done to evaluate the safety, tolerability and potential effectiveness of&#xD;
      a new investigational drug, bryostatin 1, in patients with Alzheimer's disease (AD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a single center, randomized, double-blind, placebo-controlled, parallel groups&#xD;
      trial in patients with AD. Each subject enrolled in the trial will be randomized to receive a&#xD;
      single IV dose of 0 (placebo) or 25 μg/m2 bryostatin. A total of 15 subjects (5 in the&#xD;
      placebo arm and 10 in the treatment arm) will be enrolled in the study. The study consists of&#xD;
      screening evaluations and on study evaluations divided into two segments, an inpatient&#xD;
      segment and an outpatient segment. The four-day inpatient segment will consist of baseline&#xD;
      evaluations and a 1-hour IV infusion of study drug followed by evaluations at multiple&#xD;
      evaluations over the first 72 hrs post dose. During the outpatient segment, patients will be&#xD;
      followed for AEs and have a final evaluation at 2 weeks post dose and a 4-week telephone&#xD;
      safety follow up. Evaluations will include safety, efficacy, pharmacokinetics, and&#xD;
      pharmacodynamics as assessed by PKC activity&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Part 2 of study replaced by NTRP-101-202, assessing 3 doses of bryostatin.&#xD;
  </why_stopped>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>Within 2 weeks of study drug dosing</time_frame>
    <description>Evaluate the safety and tolerability of bryostatin 1 (hereinafter referred to as bryostatin) in patients with Alzheimer's Disease (AD) following a single intravenous (IV) dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD</measure>
    <time_frame>48 hours post start of study drug infusion</time_frame>
    <description>Hopkins Verbal Learning Test - Revised (HVLT-R) delayed recall; change from baseline. HVLT consists of a 12-item word list drawn from 3 semantic categories, presented in 3 learning trials. Score range = 0-12. The lower the number, the more impaired.&#xD;
Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Total Score Range: 0-20. Each portion of the drawing is scored 1 point for correctness and completeness and 1 point for being placed properly in relation to the rest of the drawing. Drawing and placement scores are summed for the item total. To obtain subtest total score, the drawing and placement scores are summed for each item. The lower the number, the more impaired.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD</measure>
    <time_frame>Specified timepoints within 2 weeks post study drug infusion</time_frame>
    <description>HVLT-R (Hopkins Verbal Learning Test-Revised™) delayed recall (change from baseline). A 12-item word list: 3 learning trials. Score range = 0-12. The lower the number, the more impaired.&#xD;
Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Score Range: 0-20. The lower the number, the more impaired. Digit Symbol Coding (observed), Score range: 0-125. The lower the number, the more impaired.&#xD;
Clinical Dementia Rating- Sum of Boxes (CDR-SB, observed). Sum of 6 investigated domains (Memory, Orientation, Judgment and Problem Solving, Community Affairs, Home and Hobbies, Personal Care). Each subtest range is 0-3; Sum of all 6 subtest scores gives total CDR-SB score (range= 0-18).The higher the number, the more impaired.&#xD;
Mini Mental State Exam, version 2 (MMSE-2), change from baseline. The MMSE-2 measures aspects of cognitionon a scale of 0-30. Lower scores indicate greater cognitive impairment.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pharmacokinetic Parameters of Bryostatin.</measure>
    <time_frame>Bryostatin plasma concentration pre-dose and at 15 min, 30 min, 1 hr, 1.5 hr, 2hr, 3hr and 6rs post dose.</time_frame>
    <description>Preliminary evaluation of pharmacokinetics and pharmacodynamics (Cmax, Tmax, AUClast).</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Alzheimer's Disease</condition>
  <arm_group>
    <arm_group_label>Bryostatin 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>single dose of placebo, intravenous infusion over 1 hour</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bryostatin 1</intervention_name>
    <description>25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.</description>
    <arm_group_label>Bryostatin 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo, single dose via intravenous infusion over 1 hour.</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, age 50 - 85 yrs. Females are non-childbearing potential&#xD;
&#xD;
          -  Patient must have a cognitive deficit present for at least 1 year and meet diagnostic&#xD;
             criteria for probable Alzheimer's Disease Dementia by NIA-AA criteria or prodromal&#xD;
             Alzheimer's Disease&#xD;
&#xD;
          -  Mini Mental State Exam score of 16-26&#xD;
&#xD;
          -  Ability to walk, at least with an assistive device&#xD;
&#xD;
          -  Vision and hearing sufficient to comply with testing&#xD;
&#xD;
          -  Normal cognitive and social functioning prior to onset of dementia, with evidence of&#xD;
             progressive symptoms from patient or informant&#xD;
&#xD;
          -  Consistent caregiver to accompany patient to visits&#xD;
&#xD;
          -  Sufficient basic education to be able to complete the cognitive assessments&#xD;
&#xD;
          -  Living outside an institution&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Dementia due to any condition other than AD, including vascular dementia&#xD;
&#xD;
          -  Significant neuroimaging abnormalities, previously known or discovered on screening&#xD;
             MRI scan,&#xD;
&#xD;
          -  Evidence of clinically significant unstable cardiovascular, renal, hepatic,&#xD;
             gastrointestinal, neurological, or metabolic disease within the past 6 months&#xD;
&#xD;
          -  Use of any drug within 14 days prior to randomization unless the dose of the drug and&#xD;
             the condition being treated have been stable for at least 30 days and are expected to&#xD;
             remain stable during the study&#xD;
&#xD;
          -  Use of tobacco products or nicotine-containing products within 3 months before Day 1&#xD;
&#xD;
          -  Use of high dose vitamin E, or valproic acid&#xD;
&#xD;
          -  Any medical or psychiatric condition that may require medication or surgical treatment&#xD;
             during the study&#xD;
&#xD;
          -  Life expectancy less than 6 months&#xD;
&#xD;
          -  Use of an investigational drug within 2 months prior to the screening visit&#xD;
&#xD;
          -  Clinically significant neurological disease other than AD&#xD;
&#xD;
          -  Major depression, alcohol or drug dependence or suicidality&#xD;
&#xD;
          -  Psychotic episodes requiring hospitalization or antipsychotic therapy for more than 2&#xD;
             weeks within the past 10 years, not linked to AD&#xD;
&#xD;
          -  Agitation sufficient to preclude participation in this trial&#xD;
&#xD;
          -  Epilepsy or anti-epileptic drug therapy&#xD;
&#xD;
          -  Abnormal laboratory tests that might point to another etiology for dementia;&#xD;
&#xD;
          -  Acute or poorly controlled medical illness&#xD;
&#xD;
          -  Likelihood, according to clinical judgment, of being transferred to a nursing home&#xD;
             within 6 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hakop Gevorkyan, MD, MBA</last_name>
    <role>Principal Investigator</role>
    <affiliation>California Clinical Trials Medical Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>California Clinical Trials 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>October 2017</verification_date>
  <study_first_submitted>July 2, 2014</study_first_submitted>
  <study_first_submitted_qc>August 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2014</study_first_posted>
  <results_first_submitted>March 21, 2016</results_first_submitted>
  <results_first_submitted_qc>March 21, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">April 21, 2016</results_first_posted>
  <last_update_submitted>October 3, 2017</last_update_submitted>
  <last_update_submitted_qc>October 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alzheimer's</keyword>
  <keyword>bryostatin</keyword>
  <keyword>PKC epsilon</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bryostatin 1</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Bryostatin 1</title>
          <description>single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour&#xD;
Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>single dose of placebo, intravenous infusion over 1 hour&#xD;
Placebo: Placebo, single dose via intravenous infusion over 1 hour.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Bryostatin 1</title>
          <description>single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour&#xD;
Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>single dose of placebo, intravenous infusion over 1 hour&#xD;
Placebo: Placebo, single dose via intravenous infusion over 1 hour.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="9"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="72.5" spread="8.04"/>
                    <measurement group_id="B2" value="70.7" spread="7.23"/>
                    <measurement group_id="B3" value="71.9" spread="7.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Adverse Events as a Measure of Safety and Tolerability</title>
        <description>Evaluate the safety and tolerability of bryostatin 1 (hereinafter referred to as bryostatin) in patients with Alzheimer's Disease (AD) following a single intravenous (IV) dose.</description>
        <time_frame>Within 2 weeks of study drug dosing</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bryostatin 1</title>
            <description>single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour&#xD;
Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>single dose of placebo, intravenous infusion over 1 hour&#xD;
Placebo: Placebo, single dose via intravenous infusion over 1 hour.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events as a Measure of Safety and Tolerability</title>
          <description>Evaluate the safety and tolerability of bryostatin 1 (hereinafter referred to as bryostatin) in patients with Alzheimer's Disease (AD) following a single intravenous (IV) dose.</description>
          <units>event</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Headache</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rash Papular</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD</title>
        <description>Hopkins Verbal Learning Test - Revised (HVLT-R) delayed recall; change from baseline. HVLT consists of a 12-item word list drawn from 3 semantic categories, presented in 3 learning trials. Score range = 0-12. The lower the number, the more impaired.&#xD;
Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Total Score Range: 0-20. Each portion of the drawing is scored 1 point for correctness and completeness and 1 point for being placed properly in relation to the rest of the drawing. Drawing and placement scores are summed for the item total. To obtain subtest total score, the drawing and placement scores are summed for each item. The lower the number, the more impaired.</description>
        <time_frame>48 hours post start of study drug infusion</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bryostatin 1</title>
            <description>Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo: Placebo, single dose via intravenous infusion over 1 hour.</description>
          </group>
        </group_list>
        <measure>
          <title>Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD</title>
          <description>Hopkins Verbal Learning Test - Revised (HVLT-R) delayed recall; change from baseline. HVLT consists of a 12-item word list drawn from 3 semantic categories, presented in 3 learning trials. Score range = 0-12. The lower the number, the more impaired.&#xD;
Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Total Score Range: 0-20. Each portion of the drawing is scored 1 point for correctness and completeness and 1 point for being placed properly in relation to the rest of the drawing. Drawing and placement scores are summed for the item total. To obtain subtest total score, the drawing and placement scores are summed for each item. The lower the number, the more impaired.</description>
          <units>units on a scale, change from baseline</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HVLT-R at 48hrs (change from baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="2.16"/>
                    <measurement group_id="O2" value="3.7" spread="1.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RBANS figure recall at 48hrs (CBL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" spread="4.14"/>
                    <measurement group_id="O2" value="6.7" spread="3.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD</title>
        <description>HVLT-R (Hopkins Verbal Learning Test-Revised™) delayed recall (change from baseline). A 12-item word list: 3 learning trials. Score range = 0-12. The lower the number, the more impaired.&#xD;
Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Score Range: 0-20. The lower the number, the more impaired. Digit Symbol Coding (observed), Score range: 0-125. The lower the number, the more impaired.&#xD;
Clinical Dementia Rating- Sum of Boxes (CDR-SB, observed). Sum of 6 investigated domains (Memory, Orientation, Judgment and Problem Solving, Community Affairs, Home and Hobbies, Personal Care). Each subtest range is 0-3; Sum of all 6 subtest scores gives total CDR-SB score (range= 0-18).The higher the number, the more impaired.&#xD;
Mini Mental State Exam, version 2 (MMSE-2), change from baseline. The MMSE-2 measures aspects of cognitionon a scale of 0-30. Lower scores indicate greater cognitive impairment.</description>
        <time_frame>Specified timepoints within 2 weeks post study drug infusion</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bryostatin 1</title>
            <description>Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo: single dose via intravenous infusion over 1 hour.</description>
          </group>
        </group_list>
        <measure>
          <title>Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD</title>
          <description>HVLT-R (Hopkins Verbal Learning Test-Revised™) delayed recall (change from baseline). A 12-item word list: 3 learning trials. Score range = 0-12. The lower the number, the more impaired.&#xD;
Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Score Range: 0-20. The lower the number, the more impaired. Digit Symbol Coding (observed), Score range: 0-125. The lower the number, the more impaired.&#xD;
Clinical Dementia Rating- Sum of Boxes (CDR-SB, observed). Sum of 6 investigated domains (Memory, Orientation, Judgment and Problem Solving, Community Affairs, Home and Hobbies, Personal Care). Each subtest range is 0-3; Sum of all 6 subtest scores gives total CDR-SB score (range= 0-18).The higher the number, the more impaired.&#xD;
Mini Mental State Exam, version 2 (MMSE-2), change from baseline. The MMSE-2 measures aspects of cognitionon a scale of 0-30. Lower scores indicate greater cognitive impairment.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HVLT-R 24hr Delayed Recall (change from baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" spread="3.27"/>
                    <measurement group_id="O2" value="1.3" spread="2.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HVLT-R 2 Wks Delayed Recall (change from baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="1.63"/>
                    <measurement group_id="O2" value="2.3" spread="2.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RBANS 24hr Figure Recall (change from baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" spread="4.76"/>
                    <measurement group_id="O2" value="6.0" spread="2.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RBANS 2 Wks Figure Recall (CBL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2" spread="5.60"/>
                    <measurement group_id="O2" value="7.3" spread="3.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HVLT-R delayed recall of stimuli at 48hr (CBL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2" spread="1.17"/>
                    <measurement group_id="O2" value="2.7" spread="2.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Digit Symbol Coding baseline (observed)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.2" spread="9.13"/>
                    <measurement group_id="O2" value="42.3" spread="12.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Digit Symbol Coding 24hrs post start of infusion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.0" spread="10.75"/>
                    <measurement group_id="O2" value="49.0" spread="4.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Digit Symbol Coding 48hrs post start of infusion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.3" spread="11.64"/>
                    <measurement group_id="O2" value="53.7" spread="4.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Digit Symbol Coding 2 wks post start of infusion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.3" spread="7.61"/>
                    <measurement group_id="O2" value="52.7" spread="6.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CDR, CDR-SB baseline (observed)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="0.98"/>
                    <measurement group_id="O2" value="0.7" spread="0.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CDR, CDR-SB 2wks (observed)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="1.00"/>
                    <measurement group_id="O2" value="0.7" spread="0.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MMSE-2 3hrs post start of inf (change)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" spread="1.72"/>
                    <measurement group_id="O2" value="-1.0" spread="2.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Digit Symbol Coding baseline (observed)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.2" spread="9.13"/>
                    <measurement group_id="O2" value="42.3" spread="12.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Digit Symbol Coding 3hrs post start of inf (observ</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.7" spread="6.86"/>
                    <measurement group_id="O2" value="45.3" spread="11.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MMSE-2 at 72hrs (change from Baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" spread="1.52"/>
                    <measurement group_id="O2" value="3.3" spread="2.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MMSE-2 at 2wks (change from Baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3" spread="1.86"/>
                    <measurement group_id="O2" value="4.7" spread="1.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Pharmacokinetic Parameters of Bryostatin.</title>
        <description>Preliminary evaluation of pharmacokinetics and pharmacodynamics (Cmax, Tmax, AUClast).</description>
        <time_frame>Bryostatin plasma concentration pre-dose and at 15 min, 30 min, 1 hr, 1.5 hr, 2hr, 3hr and 6rs post dose.</time_frame>
        <population>Subjects who received a single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour (PK population)</population>
        <group_list>
          <group group_id="O1">
            <title>Bryostatin 1</title>
            <description>Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo: Placebo, single dose via intravenous infusion over 1 hour.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Parameters of Bryostatin.</title>
          <description>Preliminary evaluation of pharmacokinetics and pharmacodynamics (Cmax, Tmax, AUClast).</description>
          <population>Subjects who received a single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour (PK population)</population>
          <units>bryostatin plasma concentration (ng/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>predose Bryostatin Plasma Concentration (ng/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Concentration 15 min post (ng/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.880" spread="0.133"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Concentration 30 min post (ng/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.941" spread="0.168"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Concentration 1 hr post (ng/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.04" spread="0.309"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Concentration 1.5 hrs post (ng/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.181" spread="0.148"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Concentration 2 hrs post (ng/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0702" spread="0.109"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Concentration 3 hrs post (ng/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Concentration 6 hrs post (ng/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cmax (ng/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.09" spread="0.246"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Bryostatin plasma concentration: mean Tmax (h)</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>mean Tmax(h)</param_type>
            <param_value>0.920</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>SD=0.206</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Bryostatin plasma concentration AUC0-last (h*ng/mL)</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>mean (h*ng/mL)</param_type>
            <param_value>1.05</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>SD=0.330</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event collection began 28 days prior to dosing and continued until 4 weeks after dosing. Ongoing AEs were followed until resolved or stabilized.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Bryostatin 1</title>
          <description>single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour&#xD;
Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>single dose of placebo, intravenous infusion over 1 hour&#xD;
Placebo: Placebo, single dose via intravenous infusion over 1 hour.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash Papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>PI cannot disclose trial results without permission from sponsor.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Vice President, Regulatory Affairs</name_or_title>
      <organization>Neurotrope BioScience, Inc</organization>
      <phone>973-826-5109</phone>
      <email>dcrockford@neurotropebioscience.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02221947
org study id: NTRP101-201
nct id: NCT02221947
lead sponsor: 
collaborator: 
has dmc: No
This study is being done to evaluate the safety, tolerability and potential effectiveness of
      a new investigational drug, bryostatin 1, in patients with Alzheimer's disease (AD).
This study is a single center, randomized, double-blind, placebo-controlled, parallel groups
      trial in patients with AD. Each subject enrolled in the trial will be randomized to receive a
      single IV dose of 0 (placebo) or 25 μg/m2 bryostatin. A total of 15 subjects (5 in the
      placebo arm and 10 in the treatment arm) will be enrolled in the study. The study consists of
      screening evaluations and on study evaluations divided into two segments, an inpatient
      segment and an outpatient segment. The four-day inpatient segment will consist of baseline
      evaluations and a 1-hour IV infusion of study drug followed by evaluations at multiple
      evaluations over the first 72 hrs post dose. During the outpatient segment, patients will be
      followed for AEs and have a final evaluation at 2 weeks post dose and a 4-week telephone
      safety follow up. Evaluations will include safety, efficacy, pharmacokinetics, and
      pharmacodynamics as assessed by PKC activity
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
time frame: Within 2 weeks of study drug dosing
description: Evaluate the safety and tolerability of bryostatin 1 (hereinafter referred to as bryostatin) in patients with Alzheimer's Disease (AD) following a single intravenous (IV) dose.
measure: Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
time frame: 48 hours post start of study drug infusion
description: Hopkins Verbal Learning Test - Revised (HVLT-R) delayed recall; change from baseline. HVLT consists of a 12-item word list drawn from 3 semantic categories, presented in 3 learning trials. Score range = 0-12. The lower the number, the more impaired.
Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Total Score Range: 0-20. Each portion of the drawing is scored 1 point for correctness and completeness and 1 point for being placed properly in relation to the rest of the drawing. Drawing and placement scores are summed for the item total. To obtain subtest total score, the drawing and placement scores are summed for each item. The lower the number, the more impaired.
measure: Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
time frame: Specified timepoints within 2 weeks post study drug infusion
description: HVLT-R (Hopkins Verbal Learning Test-Revised™) delayed recall (change from baseline). A 12-item word list: 3 learning trials. Score range = 0-12. The lower the number, the more impaired.
Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Score Range: 0-20. The lower the number, the more impaired. Digit Symbol Coding (observed), Score range: 0-125. The lower the number, the more impaired.
Clinical Dementia Rating- Sum of Boxes (CDR-SB, observed). Sum of 6 investigated domains (Memory, Orientation, Judgment and Problem Solving, Community Affairs, Home and Hobbies, Personal Care). Each subtest range is 0-3; Sum of all 6 subtest scores gives total CDR-SB score (range= 0-18).The higher the number, the more impaired.
Mini Mental State Exam, version 2 (MMSE-2), change from baseline. The MMSE-2 measures aspects of cognitionon a scale of 0-30. Lower scores indicate greater cognitive impairment.
measure: Pharmacokinetic Parameters of Bryostatin.
time frame: Bryostatin plasma concentration pre-dose and at 15 min, 30 min, 1 hr, 1.5 hr, 2hr, 3hr and 6rs post dose.
description: Preliminary evaluation of pharmacokinetics and pharmacodynamics (Cmax, Tmax, AUClast).
arm group label: Bryostatin 1
arm group type: Active Comparator
description: single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour
arm group label: placebo
arm group type: Placebo Comparator
description: single dose of placebo, intravenous infusion over 1 hour
intervention type: Drug
intervention name: Bryostatin 1
description: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.
arm group label: Bryostatin 1
intervention type: Drug
intervention name: Placebo
description: Placebo, single dose via intravenous infusion over 1 hour.
arm group label: placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: 85 Years
healthy volunteers: No
last name: Hakop Gevorkyan, MD, MBA
role: Principal Investigator
affiliation: California Clinical Trials Medical Group
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Bryostatin 1
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 