<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/NCT03306329</url>
  </required_header>
  <id_info>
    <org_study_id>DNS-7801-201</org_study_id>
    <nct_id>NCT03306329</nct_id>
  </id_info>
  <brief_title>DNS-7801 vs. Placebo in Parkinson's Disease</brief_title>
  <acronym>PRIORITY</acronym>
  <official_title>A Phase 2a, Double-Blind, Placebo-Controlled Two-Part Study To Investigate the Safety and Efficacy of Increasing Doses Of DNS-7801 In Parkinson's Disease (PD) Subjects With Motor Fluctuations</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dart NeuroScience, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dart NeuroScience, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, double-blind, two-part placebo-controlled parallel group outpatient&#xD;
      treatment study that will utilize standard Parkinson's Disease measures to evaluate the&#xD;
      effect of DNS-7801&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Administrative&#xD;
  </why_stopped>
  <start_date type="Actual">September 13, 2017</start_date>
  <completion_date type="Actual">December 31, 2017</completion_date>
  <primary_completion_date type="Actual">December 31, 2017</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>Part A: Maximal change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III from predose</measure>
    <time_frame>2-days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Change in OFF time from Baseline to Day 28 on home PD diary</measure>
    <time_frame>28-days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part A: Safety of DNS-7801 evaluating the number of Treatment Emergent Adverse Events (TEAEs) at each study visit</measure>
    <time_frame>17-days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Score on the Columbia Suicide Severity Rating Scale (C-SSRS) as assessed at each study visit</measure>
    <time_frame>17-days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Tolerability of DNS-7801 assessed by discontinuation due to TEAE(s) [percent completers] at Day 10</measure>
    <time_frame>10-days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III from Baseline to Day 28</measure>
    <time_frame>28-days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Change in ON time without troublesome dyskinesia from Baseline to Day 28</measure>
    <time_frame>28-days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Change from Baseline in the Parkinson's Disease Quality of Life Questionnaire Summary Index</measure>
    <time_frame>28-days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Proportion of subjects with improvement in Clinical Global Impression of Improvement (CGI-I)</measure>
    <time_frame>28-days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Safety of DNS-7801 evaluating the number of Treatment Emergent Adverse Events (TEAEs) at each study visit</measure>
    <time_frame>35-days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Score on the Columbia Suicide Severity Rating Scale (C-SSRS) as assessed at each study visit</measure>
    <time_frame>35-days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Tolerability of DNS-7801 assessed by discontinuation due to TEAE(s) [percent completers]</measure>
    <time_frame>28-days</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>DNS-7801 (low-dose)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>DNS-7801 (high-dose)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DNS-7801 (low-dose)</intervention_name>
    <description>DNS-7801 (low-dose) tablets administered once daily.</description>
    <arm_group_label>DNS-7801 (low-dose)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DNS-7801 (high dose)</intervention_name>
    <description>DNS-7801 (high dose) tablets administered once daily.</description>
    <arm_group_label>DNS-7801 (high-dose)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablets administered once daily</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria:&#xD;
&#xD;
          -  Subjects who are diagnosed with Parkinson's disease as defined by the United Kingdom&#xD;
             PD Society Brain Bank Criteria for the Diagnosis of PD.&#xD;
&#xD;
          -  Modified Hoehn and Yahr Staging ≤ 3 in ON state.&#xD;
&#xD;
          -  Mini Mental State Examination Score ≥ 26.&#xD;
&#xD;
          -  Subjects must currently have a good response to levodopa and be receiving a stable&#xD;
             dose of levodopa ( at least 4 doses per day of standard levodopa or ≥ 3 doses per day&#xD;
             of Rytary™ (Carbidopa and levodopa Extended-Release Capsules) for at least 4 weeks&#xD;
             prior to screening).&#xD;
&#xD;
          -  Subjects must experience motor fluctuations with at least 2 hours of OFF periods each&#xD;
             day in the awake time.&#xD;
&#xD;
          -  Subjects must experience predictable early morning OFF periods.&#xD;
&#xD;
          -  Subjects must be able to come to the clinic in the practically defined OFF state.&#xD;
&#xD;
          -  Subject must have achieved the following results for home PD diary training, practice&#xD;
             diary collection, and Baseline diary recordings (PART B ONLY):&#xD;
&#xD;
               -  During a diary concordance session with an approved PD diary trainer/rater&#xD;
                  (minimum 4 hours), subject achieved at least 80% overall diary concordance,&#xD;
                  including at least 1 OFF interval.&#xD;
&#xD;
               -  Returned a valid 2-day (i.e., 2 consecutive 24-hour periods) practice home PD&#xD;
                  diary (as defined below).&#xD;
&#xD;
               -  Returned valid diary recordings preceding the Baseline Visit that indicated at&#xD;
                  least 2 hours of OFF time on each of the 2 days.&#xD;
&#xD;
          -  All anti-parkinsonian medications must be maintained at a stable dose for at least 4&#xD;
             weeks prior to the initial Screening Visit with the exception of monoamine oxidase-B&#xD;
             inhibitors, which must be maintained at a stable level for at least 8 weeks prior to&#xD;
             the screening visit.&#xD;
&#xD;
        Main Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of secondary or an atypical Parkinsonian syndrome.&#xD;
&#xD;
          -  Subject has severe disabling dyskinesia.&#xD;
&#xD;
          -  Subject has clinically significant psychosis or hallucinations or history of psychosis&#xD;
             in past 6 months.&#xD;
&#xD;
          -  History of previous neurosurgery for PD.&#xD;
&#xD;
          -  Currently or previously on Duopa/Duodopa.&#xD;
&#xD;
          -  Currently on apomorphine or have received apomorphine within 30 days prior to&#xD;
             baseline.&#xD;
&#xD;
          -  The subject has a diagnosis or history of a substance related disorder (excluding&#xD;
             nicotine and caffeine), including alcohol related disorder (Diagnostic and Statistical&#xD;
             Manual of Mental Disorders 5 criteria) during the 12 months prior to the Screening&#xD;
             Visit.&#xD;
&#xD;
          -  The subject has tested positive at the Screening Visit for drugs of abuse (e.g.,&#xD;
             opiates, cannabinoids, methadone, cocaine, and amphetamines [including ecstasy]).&#xD;
&#xD;
          -  Any medical (including acute or chronic pain), surgical, or psychiatric condition,&#xD;
             laboratory value, or concomitant medication which, in the opinion of the Investigator&#xD;
             or the eligibility reviewer, makes the subject unsuitable for study entry or&#xD;
             potentially unable to complete all aspects of the study.&#xD;
&#xD;
          -  Suicidal ideation within 1 year prior to the Screening Visit as evidenced by answering&#xD;
             &quot;yes&quot; to Questions 4 or 5 on the suicidal ideation portion of the Columbia Suicide&#xD;
             Severity Rating Scale (C-SSRS) or attempted suicide within the last 5 years.&#xD;
&#xD;
          -  Subjects with a current major depressive episode or a Beck Depression Inventory-II&#xD;
             score of &gt; 19. Subjects receiving treatment for depression with antidepressants may be&#xD;
             enrolled if they have been on a stable daily dose of the antidepressant for at least 8&#xD;
             weeks before the Baseline Visit.&#xD;
&#xD;
          -  Exposure to neuroleptics (antipsychotic drugs) for more than 1 month within the past 2&#xD;
             years, or any exposure within the past year.&#xD;
&#xD;
          -  Any malignancy in the 5 years prior to randomization (excluding basal cell carcinoma&#xD;
             of the skin or cervical carcinoma in situ that have been successfully treated).&#xD;
&#xD;
          -  Current or previous diagnosis of malignant melanoma or the presence of any suspicious&#xD;
             skin lesion based on physical exam findings.&#xD;
&#xD;
          -  Subjects, who, for any reason, are judged by the Investigator to be inappropriate for&#xD;
             this study, including subjects who are unable to communicate or cooperate with the&#xD;
             Investigator or who have/had a clinically significant illness or abnormal physical&#xD;
             examination that may compromise safety of the subject during the trial or affect&#xD;
             ability of the subject to adhere to study procedures&#xD;
&#xD;
          -  Serum creatinine &gt; 2 mg/dL.&#xD;
&#xD;
          -  Total serum bilirubin &gt; 2 mg/dL.&#xD;
&#xD;
          -  Coagulation parameters (prothrombin time, activated partial thromboplastin time and&#xD;
             international normalized ratio) and other laboratory parameters that, in the opinion&#xD;
             of the Investigator, are in a range that could be harmful to the subject.&#xD;
&#xD;
          -  Subjects with alanine transaminase or aspartate transaminase ≥ 3x upper limit of&#xD;
             normal at Screening.&#xD;
&#xD;
          -  Uncontrolled hypertension (e.g., Stage 2 hypertension - systolic &gt; 160 mm Hg or&#xD;
             diastolic &gt; 100 mm Hg).&#xD;
&#xD;
          -  Orthostatic hypotension that is symptomatic or requires medication.&#xD;
&#xD;
          -  Subjects with heart block that, in the opinion of the Investigator, could interfere&#xD;
             with the subject's ability to participate in the study.&#xD;
&#xD;
          -  Hospitalization for myocardial infarction, ischemic heart disease, or congestive heart&#xD;
             failure within the 12 months prior to the Screening Visit.&#xD;
&#xD;
          -  Evidence on clinical examination or ECG of a clinically significant arrhythmia, as&#xD;
             assessed by the Investigator.&#xD;
&#xD;
          -  Subject is currently lactating or pregnant or planning to become pregnant during the&#xD;
             study.&#xD;
&#xD;
          -  Use of any medications that are prohibited concomitant medications during the study,&#xD;
             are known to be strong or moderate inducers or inhibitors of cytochrome P450 (CYP)&#xD;
             3A4, or are contraindicated for treatment with study drug.&#xD;
&#xD;
          -  Consumption of grapefruit containing foods or beverages within 14 days before Baseline&#xD;
             and for 14 days after the last dose of study drug.&#xD;
&#xD;
          -  Subject is currently participating in or has participated in another study of a study&#xD;
             drug or medical device in the last 3 months or within 5 half-lives of the study drug&#xD;
             (whichever is longer) prior to Baseline.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Philip Perera, MD</last_name>
    <role>Study Director</role>
    <affiliation>Dart NeuroScience, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Collaborative Neuroscience Network</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SC3 Research</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Movement Disorders Center</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkinsons Disease and Movement Disorders Center of Boca Raton</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Florida Parkinson's Disease and Movement Disorders Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Quest Research Institute</name>
      <address>
        <city>Farmington</city>
        <state>Michigan</state>
        <zip>48334</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Neurological Institute PA</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Premier Clinical Research</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>September 25, 2017</study_first_submitted>
  <study_first_submitted_qc>October 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>January 30, 2018</last_update_submitted>
  <last_update_submitted_qc>January 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2018</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>
  </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/NCT03306329
org study id: DNS-7801-201
nct id: NCT03306329
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized, double-blind, two-part placebo-controlled parallel group outpatient
      treatment study that will utilize standard Parkinson's Disease measures to evaluate the
      effect of DNS-7801
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Part A: Maximal change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III from predose
time frame: 2-days
measure: Part B: Change in OFF time from Baseline to Day 28 on home PD diary
time frame: 28-days
measure: Part A: Safety of DNS-7801 evaluating the number of Treatment Emergent Adverse Events (TEAEs) at each study visit
time frame: 17-days
measure: Part A: Score on the Columbia Suicide Severity Rating Scale (C-SSRS) as assessed at each study visit
time frame: 17-days
measure: Part A: Tolerability of DNS-7801 assessed by discontinuation due to TEAE(s) [percent completers] at Day 10
time frame: 10-days
measure: Part B: Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III from Baseline to Day 28
time frame: 28-days
measure: Part B: Change in ON time without troublesome dyskinesia from Baseline to Day 28
time frame: 28-days
measure: Part B: Change from Baseline in the Parkinson's Disease Quality of Life Questionnaire Summary Index
time frame: 28-days
measure: Part B: Proportion of subjects with improvement in Clinical Global Impression of Improvement (CGI-I)
time frame: 28-days
measure: Part B: Safety of DNS-7801 evaluating the number of Treatment Emergent Adverse Events (TEAEs) at each study visit
time frame: 35-days
measure: Part B: Score on the Columbia Suicide Severity Rating Scale (C-SSRS) as assessed at each study visit
time frame: 35-days
measure: Part B: Tolerability of DNS-7801 assessed by discontinuation due to TEAE(s) [percent completers]
time frame: 28-days
arm group label: DNS-7801 (low-dose)
arm group type: Experimental
arm group label: DNS-7801 (high-dose)
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: DNS-7801 (low-dose)
description: DNS-7801 (low-dose) tablets administered once daily.
arm group label: DNS-7801 (low-dose)
intervention type: Drug
intervention name: DNS-7801 (high dose)
description: DNS-7801 (high dose) tablets administered once daily.
arm group label: DNS-7801 (high-dose)
intervention type: Drug
intervention name: Placebo
description: Placebo tablets administered once daily
arm group label: Placebo
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: No
last name: Philip Perera, MD
role: Study Director
affiliation: Dart NeuroScience, LLC
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease