<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/NCT04407377</url>
  </required_header>
  <id_info>
    <org_study_id>CLN-116</org_study_id>
    <nct_id>NCT04407377</nct_id>
  </id_info>
  <brief_title>Effects of Tolperisone on Measures of Drowsiness and Cognitive Function</brief_title>
  <official_title>A Randomized, 4-Period, Crossover Study to Investigate the Effects of Tolperisone on Measures of Drowsiness and Cognitive Function Compared to Cyclobenzaprine and Placebo</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neurana Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Neurana Pharmaceuticals, Inc.</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>
      A Randomized, 4-Period, Crossover Study to characterize the effects of tolperisone 200 mg and&#xD;
      400 mg (supratherapeutic dose) three times a day (TID) over 3 days of dosing on measures of&#xD;
      simulated driving performance, cognitive function and drowsiness and compared to placebo and&#xD;
      cyclobenzaprine (single-day, residual effect, multiple-day).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 20, 2020</start_date>
  <completion_date type="Actual">March 31, 2021</completion_date>
  <primary_completion_date type="Actual">October 16, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Driving Performance</measure>
    <time_frame>Day 1</time_frame>
    <description>Standard Deviation of Lateral Position, measured by simulated driving performance using Cognitive Research Corporation Driving Simulator-MiniSim (CRCDS-MiniSim), of tolperisone compared to placebo</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Karolinska Sleepiness Scale</measure>
    <time_frame>Day 1</time_frame>
    <description>Measure of Drowsiness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Epworth Sleepiness Scale</measure>
    <time_frame>Day 3</time_frame>
    <description>Measure of Drowsiness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reaction Time</measure>
    <time_frame>Day 1</time_frame>
    <description>Measure of Cognitive Function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rapid Visual Information Processing</measure>
    <time_frame>Day 1</time_frame>
    <description>Measure of Cognitive Function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CogScreen Symbol Digit Coding Test</measure>
    <time_frame>Day 1</time_frame>
    <description>Measure of Cognitive Function</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Tolperisone 200 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study Drug, Tolperisone 200mg TID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tolperisone 400 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study Drug, Tolperisone 400mg TID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cyclobenzaprine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Active Comparator, Cyclobenzaprine 10mg TID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, TID</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tolperisone Hydrochloride</intervention_name>
    <description>Study Drug</description>
    <arm_group_label>Tolperisone 200 mg</arm_group_label>
    <arm_group_label>Tolperisone 400 mg</arm_group_label>
    <other_name>Tolperisone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclobenzaprine Hydrochloride 10 MG</intervention_name>
    <description>Active Comparator</description>
    <arm_group_label>Cyclobenzaprine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo Comparator</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ambulatory male or female, between 21 and 65 years of age, inclusive, for the entire&#xD;
             duration of the study (from Screening through Day 3 of last treatment period).&#xD;
&#xD;
          -  Body mass index (BMI) range between 18.5 and 30.0 kg/m2, inclusive.&#xD;
&#xD;
          -  Subject must possess a valid driver's license and be an active driver and have driven&#xD;
             a minimum of 10,000 miles (about 16,000 km) per year for the previous 3 years.&#xD;
&#xD;
          -  Subject must demonstrate simulator sickness questionnaire scores that are not&#xD;
             indicative of simulator sickness as defined in the driving simulation operations&#xD;
             manual.&#xD;
&#xD;
          -  Subject must have a regular sleep pattern, not be engaged in shift-work, and in&#xD;
             general, have at least 7 hours of sleep each night.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of sleep disorders, including insomnia, sleep apnea, Restless Legs Syndrome&#xD;
             (RLS), or narcolepsy, night-shift workers, routine daytime napping or oversleeping on&#xD;
             weekends days (off work) or a score higher than 10 on the Epworth Sleepiness Scale&#xD;
             (ESS) at Screening.&#xD;
&#xD;
          -  A history of difficulty in falling asleep or staying asleep in the previous 3 months&#xD;
             that is considered clinically significant by the Investigator.&#xD;
&#xD;
          -  Subject has traveled across 2 or more time zones (trans meridian travel) in the last 2&#xD;
             weeks prior to randomization or is expected to travel across 2 or more time zones&#xD;
             during the study.&#xD;
&#xD;
          -  Subject has any physical condition (e.g., severe vision issues, hand use limitations)&#xD;
             that would prevent the subject from performing the cognitive or drowsiness&#xD;
             assessments.&#xD;
&#xD;
          -  Subject has a presence or history of any medically diagnosed, clinically significant&#xD;
             psychiatric disorder, including depression, anxiety, insomnia, schizophrenia, or&#xD;
             bipolar disorder.&#xD;
&#xD;
          -  Consumes more than 3 cups of coffee per day.&#xD;
&#xD;
          -  Female subjects who are pregnant or lactating.&#xD;
&#xD;
          -  Any clinically significant medical abnormality, any clinically significant chronic&#xD;
             disease, or any clinically significant finding on physical examination.&#xD;
&#xD;
          -  Subject with a genotype status of poor-, ultrarapid-, or indeterminate- metabolizers&#xD;
             of cytochrome CYP2D6.&#xD;
&#xD;
          -  Subject is unable to remain in the research unit for each of the treatment periods.&#xD;
&#xD;
          -  Subject has visual or auditory impairment which in the opinion of the Investigator&#xD;
             would interfere with study related procedures or study conduct.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>CNS Trial</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hassman Research Institute</name>
      <address>
        <city>Berlin</city>
        <state>New Jersey</state>
        <zip>08009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>May 7, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>January 28, 2022</last_update_submitted>
  <last_update_submitted_qc>January 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2022</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>Sleepiness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclobenzaprine</mesh_term>
    <mesh_term>Tolperisone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04407377
org study id: CLN-116
nct id: NCT04407377
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
A Randomized, 4-Period, Crossover Study to characterize the effects of tolperisone 200 mg and
      400 mg (supratherapeutic dose) three times a day (TID) over 3 days of dosing on measures of
      simulated driving performance, cognitive function and drowsiness and compared to placebo and
      cyclobenzaprine (single-day, residual effect, multiple-day).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Driving Performance
time frame: Day 1
description: Standard Deviation of Lateral Position, measured by simulated driving performance using Cognitive Research Corporation Driving Simulator-MiniSim (CRCDS-MiniSim), of tolperisone compared to placebo
measure: Karolinska Sleepiness Scale
time frame: Day 1
description: Measure of Drowsiness
measure: Epworth Sleepiness Scale
time frame: Day 3
description: Measure of Drowsiness
measure: Reaction Time
time frame: Day 1
description: Measure of Cognitive Function
measure: Rapid Visual Information Processing
time frame: Day 1
description: Measure of Cognitive Function
measure: CogScreen Symbol Digit Coding Test
time frame: Day 1
description: Measure of Cognitive Function
arm group label: Tolperisone 200 mg
arm group type: Experimental
description: Study Drug, Tolperisone 200mg TID
arm group label: Tolperisone 400 mg
arm group type: Experimental
description: Study Drug, Tolperisone 400mg TID
arm group label: Cyclobenzaprine
arm group type: Active Comparator
description: Active Comparator, Cyclobenzaprine 10mg TID
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo, TID
intervention type: Drug
intervention name: Tolperisone Hydrochloride
description: Study Drug
arm group label: Tolperisone 200 mg
arm group label: Tolperisone 400 mg
other name: Tolperisone
intervention type: Drug
intervention name: Cyclobenzaprine Hydrochloride 10 MG
description: Active Comparator
arm group label: Cyclobenzaprine
intervention type: Other
intervention name: Placebo
description: Placebo Comparator
arm group label: Placebo
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Sleepiness
mesh term: Cyclobenzaprine
mesh term: Tolperisone
sharing ipd: No