<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/NCT01685281</url>
  </required_header>
  <id_info>
    <org_study_id>AL011</org_study_id>
    <nct_id>NCT01685281</nct_id>
  </id_info>
  <brief_title>Study Comparing Two Doses of MG01CI and Placebo in Adults With Predominantly Inattentive Attention Deficit Hyperactivity Disorder</brief_title>
  <official_title>Randomized, Double-blind, Single-center, Dose-finding Study Designed to Compare Two Doses of MG01CI (Metadoxine Extended Release) and Placebo in Adults With Predominantly Inattentive Attention Deficit Hyperactivity Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alcobra Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alcobra Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      study objectives are to compare the efficacy, safety and tolerability of two doses of MG01CI&#xD;
      (1400 mg and 700 mg) to Placebo for the treatment of symptoms in adults diagnosed with&#xD;
      PI-ADHD.&#xD;
&#xD;
      subjects will be randomly assigned in a 1:1:1 ratio to one of three treatment sequences as&#xD;
      follows:&#xD;
&#xD;
        1. week 1:1400 mg, week 2:700 mg, week 3:placebo&#xD;
&#xD;
        2. week 1:700 mg,week 2: placebo,week 3:1400 mg&#xD;
&#xD;
        3. week 1: placebo, week2:1400 mg, week 3 700 mg&#xD;
&#xD;
      The study will consist of three periods: a screening period of up to one week, a 3-week&#xD;
      double-blind treatment period, and a one-week safety follow-up period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this dose finding study is to compare two doses of MG01CI (1400 mg and 700 mg)&#xD;
      to Placebo, in adult subjects with PI-ADHD. A crossover study design will allow evaluation of&#xD;
      safety/tolerability and efficacy using validated computerized tests.&#xD;
&#xD;
      subjects will be randomly assigned in a 1:1:1 ratio to one of three treatment sequences as&#xD;
      follows:&#xD;
&#xD;
        1. week 1:1400 mg, week 2:700 mg, week 3:placebo&#xD;
&#xD;
        2. week 1:700 mg,week 2: placebo,week 3:1400 mg&#xD;
&#xD;
        3. week 1: placebo, week2:1400 mg, week 3 700 mg&#xD;
&#xD;
      Overview of Study Visits&#xD;
&#xD;
      Screening Period:&#xD;
&#xD;
      Visit 1 - Screening/Baseline Visit (up to 7 days prior to dosing)&#xD;
&#xD;
      Treatment Period:&#xD;
&#xD;
      Visit 2 - Day 0 (Randomization Visit) Visit 3 - Day 7 ± 3 days Visit 4 - Day 14 ± 3 days&#xD;
      Visit 5 - Day 21 ± 3 days&#xD;
&#xD;
      Follow-up period:&#xD;
&#xD;
      Visit 6 - Day 28 ± 3 days&#xD;
&#xD;
      Study duration for each subject will be up to 35 days .&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2013</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in TOVA ADHD score from Screening/Baseline to 4 hours post-dose;</measure>
    <time_frame>4 weeks</time_frame>
    <description>TOVA® is a computerized test that provides information about an individual's sustained attention, speed and consistency of responding, and behavioral self-regulation and executive functioning</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in CANTAB sub-scores from baseline (Visit 2) to 4 hours post-dose;</measure>
    <time_frame>4 weeks</time_frame>
    <description>The CANTAB is a computerized test assessing the key cognitive deficits present in ADHD. Sub-scores will include spatial working memory (SWM), stop signal task (SST), rapid visual information processing (RVP), and reaction time (RTI).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in TOVA sub-scores from Screening/Baseline to 4 hours post-dose</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants who withdrew early from the study due to AE</measure>
    <time_frame>5 weeks</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Adverse Events</measure>
    <time_frame>5 weeks</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>ADHD Predominantly Inattentive Type</condition>
  <arm_group>
    <arm_group_label>Metadoxine (MG01CI) 1400 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>single dose of Metadoxine (MG01CI) 1400 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metadoxine (MG01CI) 700 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single dose of Metadoxine (MG01CI) 700 mg</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</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metadoxine (MG01CI)</intervention_name>
    <description>MG01CI is an orally administered extended release formulation of metadoxine. Doses: 1400 mg and 700 mg and Placebo</description>
    <arm_group_label>Metadoxine (MG01CI) 1400 mg</arm_group_label>
    <arm_group_label>Metadoxine (MG01CI) 700 mg</arm_group_label>
    <other_name>metadoxil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablets will be similar in appearance (color and size) to the investigational product</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult men and women, 18 to 55 years old&#xD;
&#xD;
          2. Diagnosed with predominantly inattentive ADHD based on DSM-IV criteria for ADHD as&#xD;
             assessed by the Adult ADHD Clinician Diagnostic Scale (ACDS V1.2);&#xD;
&#xD;
          3. Clinical severity of at least a moderate level (Clinical Global Impression score of 4&#xD;
             or above)&#xD;
&#xD;
          4. TOVA ADHD score of -1.8 or below at Screening /Baseline&#xD;
&#xD;
          5. Women with childbearing potential must agree to use effective contraceptive and have&#xD;
             negative urine pregnancy test at screening visit&#xD;
&#xD;
          6. Able to attend the clinic regularly and reliably&#xD;
&#xD;
          7. Able to swallow tablets/capsules&#xD;
&#xD;
          8. Able to understand, read, write and speak Hebrew fluently to complete study related&#xD;
             materials&#xD;
&#xD;
          9. Able to understand and sign written informed consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with ADHD not otherwise specified (NOS) diagnosis&#xD;
&#xD;
          2. Subjects with combined type or predominantly hyperactive impulsive ADHD diagnoses&#xD;
&#xD;
          3. Subjects with current Axis I diagnosis on SCID&#xD;
&#xD;
          4. Subjects with lifetime bipolar or psychosis&#xD;
&#xD;
          5. Subjects in treatment for Axis I disorders, even if the disorder is remitted&#xD;
&#xD;
          6. Subjects who were non-responders to at least two adequately administered ADHD&#xD;
             treatments&#xD;
&#xD;
          7. Subjects with any medical or psychiatric condition common diseases such as&#xD;
             hypertension, type 2 diabetes mellitus, hyperlipidemia, etc. are allowed per the&#xD;
             Investigator's judgment, as long as they are stable and controlled by medical therapy&#xD;
             that is constant for at least 8 weeks prior to randomization and throughout the study&#xD;
&#xD;
          8. Any prescription or non-prescription ADHD medications during the 14 days (for&#xD;
             stimulants) or 28 days (for non-stimulants and other psychotropics) prior to the&#xD;
             screening visit&#xD;
&#xD;
          9. Known or suspected HIV-positive or with advanced diseases such as AIDS, Hepatitis C,&#xD;
             Hepatitis B or tuberculosis&#xD;
&#xD;
         10. History of allergy or sensitivity to B complex vitamins&#xD;
&#xD;
         11. History or suspicion of PDD, NLD or other psychotic conditions&#xD;
&#xD;
         12. Use of Vitamin B throughout the study (either alone or in any multi-vitamin)&#xD;
&#xD;
         13. Use of ADHD medications throughout the study&#xD;
&#xD;
         14. Use of any psychotropic medications throughout the study&#xD;
&#xD;
         15. Use of investigational medication/treatment in the past 30 days prior to the screening&#xD;
             visit&#xD;
&#xD;
         16. Use of any medication or food supplement unless cleared by the medical monitor during&#xD;
             the 14-day period before randomization&#xD;
&#xD;
         17. Current (or history within the last 6 months) of drug dependence or substance abuse&#xD;
             disorder according to DSM-IV-TR criteria (excluding nicotine). Subjects should also&#xD;
             agree to refrain from significantly changing consumption of caffeine during the study.&#xD;
&#xD;
         18. Suicidality, defined as active ideation, intent or plan, or any lifetime attempt&#xD;
             (CSSRS)&#xD;
&#xD;
         19. Subjects who cannot complete any study instruments or questionnaires&#xD;
&#xD;
         20. Any relation to the Sponsor, Investigator or study staff&#xD;
&#xD;
         21. Any condition, which in the opinion of the Principal Investigator would place the&#xD;
             subject at risk or influence the conduct of the study or interpretation of results,&#xD;
             including (but not limited to) abnormally low intellectual capacity.&#xD;
&#xD;
         22. Subjects who cannot fully comprehend the implications of the protocol or comply with&#xD;
             its requirements or are capable to follow the study schedule for any reason&#xD;
&#xD;
         23. Women of childbearing potential must test negative for pregnancy at the time of&#xD;
             enrollment based on a serum pregnancy test and agree to use a reliable method of birth&#xD;
             control (e.g., oral contraceptives or Norplant®; a reliable barrier method of birth&#xD;
             control [diaphragms with contraceptive jelly; cervical caps with contraceptive jelly;&#xD;
             condoms with contraceptive foam]; intrauterine devices; partner with vasectomy; or&#xD;
             abstinence) during the study. Note that this inclusion criterion applies only to&#xD;
             females of childbearing potential. Females of childbearing potential are defined as&#xD;
             women not surgically sterilized and between menarche and 2 years post-menopause&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Iris Manor, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Geha Medical center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Geha Medical Centre</name>
      <address>
        <city>Petah Tiqva</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>January 2014</verification_date>
  <study_first_submitted>September 12, 2012</study_first_submitted>
  <study_first_submitted_qc>September 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 14, 2012</study_first_posted>
  <last_update_submitted>January 13, 2014</last_update_submitted>
  <last_update_submitted_qc>January 13, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 14, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ADHD , Inattention</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Attention Deficit Disorder with Hyperactivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metadoxine</mesh_term>
  </intervention_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/NCT01685281
org study id: AL011
nct id: NCT01685281
lead sponsor: 
has dmc: No
study objectives are to compare the efficacy, safety and tolerability of two doses of MG01CI
      (1400 mg and 700 mg) to Placebo for the treatment of symptoms in adults diagnosed with
      PI-ADHD.

      subjects will be randomly assigned in a 1:1:1 ratio to one of three treatment sequences as
      follows:

        1. week 1:1400 mg, week 2:700 mg, week 3:placebo

        2. week 1:700 mg,week 2: placebo,week 3:1400 mg

        3. week 1: placebo, week2:1400 mg, week 3 700 mg

      The study will consist of three periods: a screening period of up to one week, a 3-week
      double-blind treatment period, and a one-week safety follow-up period.
The purpose of this dose finding study is to compare two doses of MG01CI (1400 mg and 700 mg)
      to Placebo, in adult subjects with PI-ADHD. A crossover study design will allow evaluation of
      safety/tolerability and efficacy using validated computerized tests.

      subjects will be randomly assigned in a 1:1:1 ratio to one of three treatment sequences as
      follows:

        1. week 1:1400 mg, week 2:700 mg, week 3:placebo

        2. week 1:700 mg,week 2: placebo,week 3:1400 mg

        3. week 1: placebo, week2:1400 mg, week 3 700 mg

      Overview of Study Visits

      Screening Period:

      Visit 1 - Screening/Baseline Visit (up to 7 days prior to dosing)

      Treatment Period:

      Visit 2 - Day 0 (Randomization Visit) Visit 3 - Day 7 ± 3 days Visit 4 - Day 14 ± 3 days
      Visit 5 - Day 21 ± 3 days

      Follow-up period:

      Visit 6 - Day 28 ± 3 days

      Study duration for each subject will be up to 35 days .
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in TOVA ADHD score from Screening/Baseline to 4 hours post-dose;
time frame: 4 weeks
description: TOVA® is a computerized test that provides information about an individual's sustained attention, speed and consistency of responding, and behavioral self-regulation and executive functioning
measure: Change in CANTAB sub-scores from baseline (Visit 2) to 4 hours post-dose;
time frame: 4 weeks
description: The CANTAB is a computerized test assessing the key cognitive deficits present in ADHD. Sub-scores will include spatial working memory (SWM), stop signal task (SST), rapid visual information processing (RVP), and reaction time (RTI).
measure: Change in TOVA sub-scores from Screening/Baseline to 4 hours post-dose
time frame: 4 weeks
measure: Number of participants who withdrew early from the study due to AE
time frame: 5 weeks
measure: Number of Adverse Events
time frame: 5 weeks
arm group label: Metadoxine (MG01CI) 1400 mg
arm group type: Active Comparator
description: single dose of Metadoxine (MG01CI) 1400 mg
arm group label: Metadoxine (MG01CI) 700 mg
arm group type: Active Comparator
description: Single dose of Metadoxine (MG01CI) 700 mg
arm group label: Placebo
arm group type: Placebo Comparator
description: Single dose of Placebo
intervention type: Drug
intervention name: Metadoxine (MG01CI)
description: MG01CI is an orally administered extended release formulation of metadoxine. Doses: 1400 mg and 700 mg and Placebo
arm group label: Metadoxine (MG01CI) 1400 mg
arm group label: Metadoxine (MG01CI) 700 mg
other name: metadoxil
intervention type: Drug
intervention name: Placebo
description: Placebo tablets will be similar in appearance (color and size) to the investigational product
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Iris Manor, Dr.
role: Principal Investigator
affiliation: Geha Medical center
facility: 
country: Israel
responsible party type: Sponsor
mesh term: Attention Deficit Disorder with Hyperactivity
mesh term: Metadoxine