<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/NCT02238626</url>
  </required_header>
  <id_info>
    <org_study_id>MN-166-ALS-1201</org_study_id>
    <nct_id>NCT02238626</nct_id>
  </id_info>
  <brief_title>Ibudilast (MN-166) in Subjects With Amyotrophic Lateral Sclerosis (ALS)</brief_title>
  <acronym>IBU-ALS-1201</acronym>
  <official_title>A Single-center, Randomized, Double-blind, Placebo-controlled, 6-month Trial Followed by an Open-label Extension to Evaluate the Safety, Tolerability and Clinical Endpoint Responsiveness of Ibudilast (MN-166) in Subjects With (ALS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MediciNova</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>MediciNova</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single center, randomized, double-blind, placebo-controlled, 6-month study designed&#xD;
      to evaluate the safety, tolerability and clinical responsiveness of MN-166/ibudilast (60&#xD;
      mg/day) when administered as an adjunct to riluzole (100 mg/day) in 60 subjects with ALS.&#xD;
&#xD;
      This study will consist of two treatment arms, MN-166 and matching placebo. Randomization&#xD;
      will occur in a 2:1 ratio (MN- 166: placebo).&#xD;
&#xD;
      Duration of Treatment: Screening Phase: up to 3 months; Double-blind Phase: 6 months;&#xD;
      Open-label Phase 6 months (for placebo subjects only); Follow-up Phase: 2 weeks after last&#xD;
      dose.&#xD;
&#xD;
      During treatment phase, subjects return to the clinic at Months 3 and 6 and will be&#xD;
      telephoned by staff at Months 1,2,4, and 5 to collect information about side effects and new&#xD;
      or concomitant medications.&#xD;
&#xD;
      All subjects (subjects who complete the Double-blind Phase and subjects who complete the&#xD;
      Open-label Phase) or prematurely discontinue will return for a follow-up visit approximately&#xD;
      2 weeks after the last dose of study drug to assess adverse event status and to document&#xD;
      concomitant medications.&#xD;
&#xD;
      Safety will be assessed by monitoring and recording all treatment-emergent adverse events&#xD;
      (TEAEs) including serious adverse events (SAEs) and discontinuations due to TEAEs. Additional&#xD;
      assessments will include regular monitoring of hematology, blood chemistry, and urine values,&#xD;
      regular measurement of vital signs, ECGs, medical history, physical and neurological&#xD;
      examinations.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">August 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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and Tolerability of MN-166 60 mg/d Versus Placebo When Administered With Riluzole in Subjects With ALS</measure>
    <time_frame>6 months</time_frame>
    <description>Safety will be assessed by monitoring and recording all treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs) and discontinuations due to TEAEs and Additional assessments will include regular monitoring of hematology, blood chemistry, and urine values, regular measurement of vital signs, ECGs, medical history, physical and neurological examinations.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Total Score From Baseline to Month 6</measure>
    <time_frame>6 months</time_frame>
    <description>Functional activity as assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised from baseline visit to Month 6. The best possible score is 48; the worst possible score is 0. Typically, ALS scores decline. In this outcome, the change in score will be a negative value, e.g., -4, -8, etc. The higher negative value indicates greater decline in functional activity (change in score -8 is worse than change in score -4).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory Function</measure>
    <time_frame>6 months</time_frame>
    <description>Change in respiratory function (breathing capacity) from baseline to Month 6, as measured by slow vital capacity, in which the patient breathes into a spirometer slowly until the lungs are cleared of air. SVC is measured in liters (L). The greater the mean change from baseline to 6 months, the worse the outcome. For example, -10 is worse than -6.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle Strength</measure>
    <time_frame>6 months</time_frame>
    <description>Muscle strength measured by manual muscle testing (MMT) and instrumented hand-held dynamometry. Maximum muscle strength is assessed by measuring the best of 2 handgrips represented as kilograms (kg). The greater the change from baseline to month 6, the worse off the subject is. For example, a change of -0.50 is worse than -0.40.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of Non-invasive Ventilation</measure>
    <time_frame>6 months</time_frame>
    <description>Non-invasive ventilation (NIV) utilization measured by clinically indicated prescription for NIV intervention and time to clinically indicated prescription for NIV intervention in each group (for early ALS subjects only). This is intended to count the number of subjects who had to go on non-invasive ventilation, as prescribed by the Principal Investigator, during study participation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Mean Change in Baseline to Month 6 in Quality of Life as Measured by the Amyotrophic Lateral Sclerosis Assessment Questionnaire - 5</measure>
    <time_frame>6 months</time_frame>
    <description>A patient self-reported questionnaire specifically designed to measure 5 areas of health: physical mobility, activities of daily living and independence, eating and drinking, communication, and emotional functioning. The ALSAQ-5 is brief and easy to complete questionnaire and has undergone rigorous testing for validity, reliability, and sensitivity to change and has been shown to be a robust tool for assessing ALS. The lowest possible score is 0 and the highest possible score is 20. The greater the mean decrease from baseline to Month 6, the group was considered worse off. For example, -2 is worse than -1. The greater the mean increase from baseline to Month 6, the group was considered improved. For example, 2 is better than 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression of Change (CGIC)</measure>
    <time_frame>6 months</time_frame>
    <description>A scale used to provide a global rating of illness severity, improvement, and response to treatment. It is a 3-item observer rating scale and uses a 7-point rating scale. The scale was rated relative to the previous standard of care visit prior to randomization for entry, i.e., -3 much much much worse, -2 much much worse, - 1 much worse, 0 no change, +1 much better, +2 much much better, +3 much, much, much better. Ratings were provided by the Investigator. The greater the mean decrease from baseline to Month 6, the group was considered worse off. For example, -2 is worse than -1. The greater the mean increase from baseline to Month 6, the group was considered improved. For example, 2 is better than 1.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Amyotrophic Lateral Sclerosis</condition>
  <arm_group>
    <arm_group_label>Placebo (for MN-166)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MN-166</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (for MN-166)</intervention_name>
    <arm_group_label>Placebo (for MN-166)</arm_group_label>
    <other_name>Sugar pill manufactured to mimic MN-166 10 mg tablet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MN-166</intervention_name>
    <arm_group_label>MN-166</arm_group_label>
    <other_name>ibudilast</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>riluzole</intervention_name>
    <description>Patient is given 50 mg riluzole twice daily.</description>
    <arm_group_label>MN-166</arm_group_label>
    <arm_group_label>Placebo (for MN-166)</arm_group_label>
    <other_name>Rilutek</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent is obtained and willing and able to comply with the protocol&#xD;
             in the opinion of the Investigator.&#xD;
&#xD;
          -  Male or female subjects ages ≥ 18 to 80 years, inclusive&#xD;
&#xD;
          -  Diagnosis of familial or sporadic ALS as defined by the El Escorial-Revised (2000)&#xD;
             research diagnostic criteria for ALS [Clinically Definite, Clinically Probable,&#xD;
             Probable-Laboratory-Supported]&#xD;
&#xD;
          -  Diagnosis of ALS with onset of less than or equal to 5 years from first clinical&#xD;
             weakness&#xD;
&#xD;
          -  Slow vital capacity ≥ 60% of predicted within 1 month prior to Treatment Day 1&#xD;
&#xD;
          -  Currently on a stable dose of riluzole for at least 30 days prior to initiation of&#xD;
             study drug. Subjects not currently taking riluzole will be started on 50 mg qd for the&#xD;
             first 7 days followed by 50 mg bid for the following 21 days prior to screening.&#xD;
             Patients may be screened during this time period but not started on study drug until&#xD;
             they are on a stable dose of riluzole.&#xD;
&#xD;
          -  All females will be considered to be of childbearing potential unless they are&#xD;
             postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age&#xD;
             group, and without other known or suspected cause) or have been sterilized surgically&#xD;
             (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all&#xD;
             with surgery at least 1 month before dosing). Females of childbearing potential must&#xD;
             use an effective method of contraception throughout the entire study period and for 30&#xD;
             days after study drug discontinuation.&#xD;
&#xD;
          -  Females must not be lactating or pregnant at Screening or Baseline (as documented by a&#xD;
             negative beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin&#xD;
             [hCG]). A separate baseline assessment is required if a negative screening pregnancy&#xD;
             test was obtained more than 72 hours before the first dose of study drug.&#xD;
&#xD;
          -  Males should practice contraception as follows: condom use and contraception by female&#xD;
             partner.&#xD;
&#xD;
          -  Able to swallow study medication capsules.&#xD;
&#xD;
          -  Subject is willing and able to comply with the protocol assessments and visits, in the&#xD;
             opinion of the study nurse/coordinator and the Investigator.&#xD;
&#xD;
          -  Has no known allergies to the study drug or its excipients.&#xD;
&#xD;
          -  Has received 23-valent pneumococcal vaccine within 4 years prior to starting clinical&#xD;
             trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of tracheostomy, tracheostomy invasive mechanical ventilation [TIMV].&#xD;
&#xD;
          -  Greater than 3% predicted loss in post-diagnosis vital capacity per month or a greater&#xD;
             than 1 unit loss in post diagnosis ALSFRS-R total score per month [ exclusive of loss&#xD;
             due to beginning use of assistive devices]&#xD;
&#xD;
          -  Confirmed hepatic insufficiency or abnormal liver function (AST and/or ALT greater&#xD;
             than 3 times the upper limit of the normal range)&#xD;
&#xD;
          -  Renal insufficiency as defined by a serum creatinine greater than 1.5 times the upper&#xD;
             limit of normal range&#xD;
&#xD;
          -  Currently has a clinically significant psychiatric disorder or dementia which would&#xD;
             preclude evaluation of symptoms.&#xD;
&#xD;
          -  Has a clinically significant medical condition (other than ALS) including the&#xD;
             following: neurological, metabolic, hepatic, renal, hematological, pulmonary,&#xD;
             cardiovascular, gastrointestinal, urological disorder, or central nervous system&#xD;
             infection that would pose a risk to the subject if they were to participate in the&#xD;
             study or that might confound the results of the study.&#xD;
&#xD;
          -  History of malignancy &lt; 5 years prior to signing the informed consent, except for&#xD;
             adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.&#xD;
&#xD;
          -  ECG finding of QTcB prolongation &gt; 450 ms for males and &gt; 470 ms for females at&#xD;
             screening&#xD;
&#xD;
          -  History of HIV (human immunodeficiency virus), clinically significant chronic&#xD;
             hepatitis, or other active infection&#xD;
&#xD;
          -  Subject has a history of stomach or intestinal surgery or any other condition that&#xD;
             could interfere with or is judged by the Investigator to interfere with absorption,&#xD;
             distribution, metabolism, or excretion of study drug.&#xD;
&#xD;
          -  Subject has a history of alcohol or substance abuse (DSM-IV-TR criteria) within 3&#xD;
             months prior to screening or alcohol or substance dependence (DSM-IV-TR criteria)&#xD;
             within 12 months prior to screening.&#xD;
&#xD;
          -  Subject has poor peripheral venous access that will limit the ability to draw blood as&#xD;
             judged by the Investigator.&#xD;
&#xD;
          -  Currently participating, or has participated in, a study with an investigational or&#xD;
             marketed compound or device within 3 months prior to signing the informed consent.&#xD;
&#xD;
          -  Unable to cooperate with any study procedures, unlikely to adhere to the study&#xD;
             procedures and keep appointments, in the opinion of the Investigator.&#xD;
&#xD;
        Advanced ALS group will follow the same inclusion/exclusion as the early ALS subjects with&#xD;
        the exception of the following:&#xD;
&#xD;
        Inclusion criteria:&#xD;
&#xD;
          -  Diagnosis of ALS with onset of ≤10 years from first clinical weakness&#xD;
&#xD;
          -  On Non-invasive ventilator with Non-invasive pressure [P-NIV] or volume [V-NIV] cycled&#xD;
             ventilation stable use for ≥ 4 hours daily for 1 month prior to Treatment Day.&#xD;
&#xD;
          -  Slow vital capacity ≥ 20% of predicted (Knudsen 1983) within 1 month prior to&#xD;
             Treatment Day 1&#xD;
&#xD;
          -  Able to swallow study medication capsules or have gastrostomy tube access for delivery&#xD;
             of contents of medication capsule.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Use of tracheostomy, tracheostomy invasive mechanical ventilation [TIMV].&#xD;
&#xD;
          -  No rate of progression exclusion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Benjamin R Brooks, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Carolinas Healthcare System, Dept. of Neurology</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28232-2861</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://carolinashealthcare.org</url>
    <description>Please call 1-844-CMC-ALS1 (1-844-262-2571) toll free for information on this trial.</description>
  </link>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>September 4, 2014</study_first_submitted>
  <study_first_submitted_qc>September 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <results_first_submitted>June 9, 2021</results_first_submitted>
  <results_first_submitted_qc>October 7, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 5, 2021</results_first_posted>
  <last_update_submitted>October 7, 2021</last_update_submitted>
  <last_update_submitted_qc>October 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>amyotrophic lateral sclerosis</keyword>
  <keyword>pharmacotherapy</keyword>
  <keyword>intervention</keyword>
  <keyword>prospective</keyword>
  <keyword>safety endpoint</keyword>
  <keyword>preliminary efficacy</keyword>
  <keyword>ibudilast</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ibudilast</mesh_term>
    <mesh_term>Riluzole</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 31, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/26/NCT02238626/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo (for MN-166) (Early ALS Cohort)</title>
          <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166)&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset is 5 years or less.</description>
        </group>
        <group group_id="P2">
          <title>MN-166 (Early ALS Cohort)</title>
          <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset is 5 years or less.</description>
        </group>
        <group group_id="P3">
          <title>Placebo (Advanced ALS Cohort)</title>
          <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166)&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset more than 5 years, but less than 10 years.</description>
        </group>
        <group group_id="P4">
          <title>MN-166 (Advanced ALS Cohort)</title>
          <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset is less than 10 years, but more than 5 years.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="34"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="20"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Early ALS Cohort: Patient ALS symptom onset 5 years or less before screening. Advanced ALS Cohort: Patient ALS symptom onset between 5 and 10 years before screening.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo (for MN-166) (Early ALS Cohort)</title>
          <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166)&#xD;
riluzole: Patient is given 50 mg riluzole twice daily.</description>
        </group>
        <group group_id="B2">
          <title>MN-166 (Early ALS Cohort)</title>
          <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166&#xD;
riluzole: Patient is given 50 mg riluzole twice daily.</description>
        </group>
        <group group_id="B3">
          <title>Placebo (for MN-166) (Advanced ALS Cohort)</title>
          <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166) riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years of Screening.</description>
        </group>
        <group group_id="B4">
          <title>MN-166 (Advanced ALS Cohort)</title>
          <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166 riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years before screening.</description>
        </group>
        <group group_id="B5">
          <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="17"/>
            <count group_id="B2" value="34"/>
            <count group_id="B3" value="8"/>
            <count group_id="B4" value="11"/>
            <count group_id="B5" value="70"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="57.2" spread="9.8"/>
                    <measurement group_id="B2" value="60.4" spread="10.9"/>
                    <measurement group_id="B3" value="56.9" spread="7.4"/>
                    <measurement group_id="B4" value="61.6" spread="8.1"/>
                    <measurement group_id="B5" value="58.9" spread="9.5"/>
                  </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="5"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="70"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="63"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Safety and Tolerability of MN-166 60 mg/d Versus Placebo When Administered With Riluzole in Subjects With ALS</title>
        <description>Safety will be assessed by monitoring and recording all treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs) and discontinuations due to TEAEs and Additional assessments will include regular monitoring of hematology, blood chemistry, and urine values, regular measurement of vital signs, ECGs, medical history, physical and neurological examinations.</description>
        <time_frame>6 months</time_frame>
        <population>Safety analysis population included all randomized subjects who received at least one dose of study drug and had at least one post-dose safety assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (for MN-166) (Early ALS Cohort)</title>
            <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166)&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years.</description>
          </group>
          <group group_id="O2">
            <title>MN-166</title>
            <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (for MN-166) (Advanced ALS Cohort)</title>
            <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166)&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years before Screening.</description>
          </group>
          <group group_id="O4">
            <title>MN-166 (Advanced ALS Cohort)</title>
            <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years before Screening.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety and Tolerability of MN-166 60 mg/d Versus Placebo When Administered With Riluzole in Subjects With ALS</title>
          <description>Safety will be assessed by monitoring and recording all treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs) and discontinuations due to TEAEs and Additional assessments will include regular monitoring of hematology, blood chemistry, and urine values, regular measurement of vital signs, ECGs, medical history, physical and neurological examinations.</description>
          <population>Safety analysis population included all randomized subjects who received at least one dose of study drug and had at least one post-dose safety assessment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="34"/>
                    <measurement group_id="O3" value="8"/>
                    <measurement group_id="O4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Total Score From Baseline to Month 6</title>
        <description>Functional activity as assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised from baseline visit to Month 6. The best possible score is 48; the worst possible score is 0. Typically, ALS scores decline. In this outcome, the change in score will be a negative value, e.g., -4, -8, etc. The higher negative value indicates greater decline in functional activity (change in score -8 is worse than change in score -4).</description>
        <time_frame>6 months</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (for MN-166) (Early ALS Cohort)</title>
            <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166)&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset within 5 years of Screening.</description>
          </group>
          <group group_id="O2">
            <title>MN-166 (Early ALS Cohort)</title>
            <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset within 5 years of screening.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (for MN-166) (Advanced ALS Cohort)</title>
            <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166)&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years of Screening.</description>
          </group>
          <group group_id="O4">
            <title>MN-166 (Advanced ALS Cohort)</title>
            <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years before screening.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Total Score From Baseline to Month 6</title>
          <description>Functional activity as assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised from baseline visit to Month 6. The best possible score is 48; the worst possible score is 0. Typically, ALS scores decline. In this outcome, the change in score will be a negative value, e.g., -4, -8, etc. The higher negative value indicates greater decline in functional activity (change in score -8 is worse than change in score -4).</description>
          <population>Safety Population</population>
          <units>score 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="17"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.8" spread="3.91"/>
                    <measurement group_id="O2" value="-4.5" spread="5.1"/>
                    <measurement group_id="O3" value="-2.2" spread="2.56"/>
                    <measurement group_id="O4" value="-4.8" spread="4.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Respiratory Function</title>
        <description>Change in respiratory function (breathing capacity) from baseline to Month 6, as measured by slow vital capacity, in which the patient breathes into a spirometer slowly until the lungs are cleared of air. SVC is measured in liters (L). The greater the mean change from baseline to 6 months, the worse the outcome. For example, -10 is worse than -6.</description>
        <time_frame>6 months</time_frame>
        <population>Subjects who completed Month 6 (double-blind treatment phase)</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (for MN-166) Early ALS Cohort</title>
            <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166)&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years of screening.</description>
          </group>
          <group group_id="O2">
            <title>MN-166 (Early ALS Cohort)</title>
            <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years of screening.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (for MN-166) (Advanced ALS Cohort)</title>
            <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166) riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years of Screening.</description>
          </group>
          <group group_id="O4">
            <title>MN-166 (Advanced ALS Cohort)</title>
            <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166 riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years before screening.</description>
          </group>
        </group_list>
        <measure>
          <title>Respiratory Function</title>
          <description>Change in respiratory function (breathing capacity) from baseline to Month 6, as measured by slow vital capacity, in which the patient breathes into a spirometer slowly until the lungs are cleared of air. SVC is measured in liters (L). The greater the mean change from baseline to 6 months, the worse the outcome. For example, -10 is worse than -6.</description>
          <population>Subjects who completed Month 6 (double-blind treatment phase)</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.1" spread="9.33"/>
                    <measurement group_id="O2" value="-10.1" spread="9.89"/>
                    <measurement group_id="O3" value="-12.2" spread="7.07"/>
                    <measurement group_id="O4" value="-11.1" spread="18.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Muscle Strength</title>
        <description>Muscle strength measured by manual muscle testing (MMT) and instrumented hand-held dynamometry. Maximum muscle strength is assessed by measuring the best of 2 handgrips represented as kilograms (kg). The greater the change from baseline to month 6, the worse off the subject is. For example, a change of -0.50 is worse than -0.40.</description>
        <time_frame>6 months</time_frame>
        <population>Subjects who completed Month 6 (double-blind treatment phase)</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (for MN-166) (Early ALS Cohort)</title>
            <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166)&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years of screening.</description>
          </group>
          <group group_id="O2">
            <title>MN-166 (Early ALS Cohort)</title>
            <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years of screening.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (for MN-166) (Advanced ALS Cohort)</title>
            <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166) riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years of Screening.</description>
          </group>
          <group group_id="O4">
            <title>MN-166 (Advanced ALS Cohort)</title>
            <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166 riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years before screening.</description>
          </group>
        </group_list>
        <measure>
          <title>Muscle Strength</title>
          <description>Muscle strength measured by manual muscle testing (MMT) and instrumented hand-held dynamometry. Maximum muscle strength is assessed by measuring the best of 2 handgrips represented as kilograms (kg). The greater the change from baseline to month 6, the worse off the subject is. For example, a change of -0.50 is worse than -0.40.</description>
          <population>Subjects who completed Month 6 (double-blind treatment phase)</population>
          <units>weight (kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.9" spread="5.37"/>
                    <measurement group_id="O2" value="-4.9" spread="5.50"/>
                    <measurement group_id="O3" value="-1.3" spread="2.37"/>
                    <measurement group_id="O4" value="-4.4" spread="3.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Use of Non-invasive Ventilation</title>
        <description>Non-invasive ventilation (NIV) utilization measured by clinically indicated prescription for NIV intervention and time to clinically indicated prescription for NIV intervention in each group (for early ALS subjects only). This is intended to count the number of subjects who had to go on non-invasive ventilation, as prescribed by the Principal Investigator, during study participation.</description>
        <time_frame>6 months</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (for MN-166) (Early ALS Cohort)</title>
            <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166)&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years of screening.</description>
          </group>
          <group group_id="O2">
            <title>MN-166 (Early ALS Cohort)</title>
            <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years of screening.</description>
          </group>
        </group_list>
        <measure>
          <title>Use of Non-invasive Ventilation</title>
          <description>Non-invasive ventilation (NIV) utilization measured by clinically indicated prescription for NIV intervention and time to clinically indicated prescription for NIV intervention in each group (for early ALS subjects only). This is intended to count the number of subjects who had to go on non-invasive ventilation, as prescribed by the Principal Investigator, during study participation.</description>
          <population>Full Analysis Set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Mean Change in Baseline to Month 6 in Quality of Life as Measured by the Amyotrophic Lateral Sclerosis Assessment Questionnaire - 5</title>
        <description>A patient self-reported questionnaire specifically designed to measure 5 areas of health: physical mobility, activities of daily living and independence, eating and drinking, communication, and emotional functioning. The ALSAQ-5 is brief and easy to complete questionnaire and has undergone rigorous testing for validity, reliability, and sensitivity to change and has been shown to be a robust tool for assessing ALS. The lowest possible score is 0 and the highest possible score is 20. The greater the mean decrease from baseline to Month 6, the group was considered worse off. For example, -2 is worse than -1. The greater the mean increase from baseline to Month 6, the group was considered improved. For example, 2 is better than 1.</description>
        <time_frame>6 months</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (for MN-166)</title>
            <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166)&#xD;
riluzole: Patient is given 50 mg riluzole twice daily.</description>
          </group>
          <group group_id="O2">
            <title>MN-166</title>
            <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166&#xD;
riluzole: Patient is given 50 mg riluzole twice daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (for MN-166) (Advanced ALS Cohort)</title>
            <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166) riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years of Screening.</description>
          </group>
          <group group_id="O4">
            <title>MN-166 (Advanced ALS Cohort)</title>
            <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166 riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years before screening.</description>
          </group>
        </group_list>
        <measure>
          <title>The Mean Change in Baseline to Month 6 in Quality of Life as Measured by the Amyotrophic Lateral Sclerosis Assessment Questionnaire - 5</title>
          <description>A patient self-reported questionnaire specifically designed to measure 5 areas of health: physical mobility, activities of daily living and independence, eating and drinking, communication, and emotional functioning. The ALSAQ-5 is brief and easy to complete questionnaire and has undergone rigorous testing for validity, reliability, and sensitivity to change and has been shown to be a robust tool for assessing ALS. The lowest possible score is 0 and the highest possible score is 20. The greater the mean decrease from baseline to Month 6, the group was considered worse off. For example, -2 is worse than -1. The greater the mean increase from baseline to Month 6, the group was considered improved. For example, 2 is better than 1.</description>
          <population>Full analysis set</population>
          <units>score 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="14"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" spread="3.00"/>
                    <measurement group_id="O2" value="1.6" spread="2.77"/>
                    <measurement group_id="O3" value="-0.70" spread="2.07"/>
                    <measurement group_id="O4" value="4.8" spread="3.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Global Impression of Change (CGIC)</title>
        <description>A scale used to provide a global rating of illness severity, improvement, and response to treatment. It is a 3-item observer rating scale and uses a 7-point rating scale. The scale was rated relative to the previous standard of care visit prior to randomization for entry, i.e., -3 much much much worse, -2 much much worse, - 1 much worse, 0 no change, +1 much better, +2 much much better, +3 much, much, much better. Ratings were provided by the Investigator. The greater the mean decrease from baseline to Month 6, the group was considered worse off. For example, -2 is worse than -1. The greater the mean increase from baseline to Month 6, the group was considered improved. For example, 2 is better than 1.</description>
        <time_frame>6 months</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (for MN-166) (Early ALS Cohort)</title>
            <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166)&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years of screening.</description>
          </group>
          <group group_id="O2">
            <title>MN-166 (Early ALS Cohort)</title>
            <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years of screening.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (for MN-166) (Advanced ALS Cohort)</title>
            <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166) riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years of Screening.</description>
          </group>
          <group group_id="O4">
            <title>MN-166 (Advanced ALS Cohort)</title>
            <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166 riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years before screening.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Global Impression of Change (CGIC)</title>
          <description>A scale used to provide a global rating of illness severity, improvement, and response to treatment. It is a 3-item observer rating scale and uses a 7-point rating scale. The scale was rated relative to the previous standard of care visit prior to randomization for entry, i.e., -3 much much much worse, -2 much much worse, - 1 much worse, 0 no change, +1 much better, +2 much much better, +3 much, much, much better. Ratings were provided by the Investigator. The greater the mean decrease from baseline to Month 6, the group was considered worse off. For example, -2 is worse than -1. The greater the mean increase from baseline to Month 6, the group was considered improved. For example, 2 is better than 1.</description>
          <population>Full analysis set</population>
          <units>score 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="14"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="0.78"/>
                    <measurement group_id="O2" value="-1.4" spread="0.75"/>
                    <measurement group_id="O3" value="-1.3" spread="0.52"/>
                    <measurement group_id="O4" value="-1.6" spread="0.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from Baseline to end of double-blind treatment (6 months).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo (for MN-166) (Early ALS Cohort)</title>
          <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166)&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years of screening.</description>
        </group>
        <group group_id="E2">
          <title>MN-166 (Early ALS Cohort)</title>
          <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166&#xD;
riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years of screening.</description>
        </group>
        <group group_id="E3">
          <title>Placebo (for MN-166) (Advanced ALS Cohort)</title>
          <description>Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.&#xD;
Placebo (for MN-166) riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years of Screening.</description>
        </group>
        <group group_id="E4">
          <title>MN-166 (Advanced ALS Cohort)</title>
          <description>MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.&#xD;
MN-166 riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years before screening.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 21.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>intestinal obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Lower limb fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>amyotrophic lateral sclerosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Ureterolithiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>pneumonia aspiration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>aspiration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 21.0</default_vocab>
        <default_assessment>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="17" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>weight decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>dysphagia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="17"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>salivary hypersecretion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>abdominal distention</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>gastrostomy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="17"/>
                <counts group_id="E2" events="12" subjects_affected="12" subjects_at_risk="34"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="17"/>
                <counts group_id="E2" events="14" subjects_affected="14" subjects_at_risk="34"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>injury</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>muscle weakness</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="17"/>
                <counts group_id="E2" events="18" subjects_affected="18" subjects_at_risk="34"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>muscle spasms</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>mobility decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>dyspnea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>respiratory distress</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>skin abrasion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>edema peripheral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director, Scientific Affairs</name_or_title>
      <organization>MediciNova, Inc.</organization>
      <phone>8583444535</phone>
      <email>makhay@medicinova.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/NCT02238626
org study id: MN-166-ALS-1201
nct id: NCT02238626
lead sponsor: 
collaborator: 
has dmc: Yes
This is a single center, randomized, double-blind, placebo-controlled, 6-month study designed
      to evaluate the safety, tolerability and clinical responsiveness of MN-166/ibudilast (60
      mg/day) when administered as an adjunct to riluzole (100 mg/day) in 60 subjects with ALS.

      This study will consist of two treatment arms, MN-166 and matching placebo. Randomization
      will occur in a 2:1 ratio (MN- 166: placebo).

      Duration of Treatment: Screening Phase: up to 3 months; Double-blind Phase: 6 months;
      Open-label Phase 6 months (for placebo subjects only); Follow-up Phase: 2 weeks after last
      dose.

      During treatment phase, subjects return to the clinic at Months 3 and 6 and will be
      telephoned by staff at Months 1,2,4, and 5 to collect information about side effects and new
      or concomitant medications.

      All subjects (subjects who complete the Double-blind Phase and subjects who complete the
      Open-label Phase) or prematurely discontinue will return for a follow-up visit approximately
      2 weeks after the last dose of study drug to assess adverse event status and to document
      concomitant medications.

      Safety will be assessed by monitoring and recording all treatment-emergent adverse events
      (TEAEs) including serious adverse events (SAEs) and discontinuations due to TEAEs. Additional
      assessments will include regular monitoring of hematology, blood chemistry, and urine values,
      regular measurement of vital signs, ECGs, medical history, physical and neurological
      examinations.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Safety and Tolerability of MN-166 60 mg/d Versus Placebo When Administered With Riluzole in Subjects With ALS
time frame: 6 months
description: Safety will be assessed by monitoring and recording all treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs) and discontinuations due to TEAEs and Additional assessments will include regular monitoring of hematology, blood chemistry, and urine values, regular measurement of vital signs, ECGs, medical history, physical and neurological examinations.
measure: Mean Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Total Score From Baseline to Month 6
time frame: 6 months
description: Functional activity as assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised from baseline visit to Month 6. The best possible score is 48; the worst possible score is 0. Typically, ALS scores decline. In this outcome, the change in score will be a negative value, e.g., -4, -8, etc. The higher negative value indicates greater decline in functional activity (change in score -8 is worse than change in score -4).
measure: Respiratory Function
time frame: 6 months
description: Change in respiratory function (breathing capacity) from baseline to Month 6, as measured by slow vital capacity, in which the patient breathes into a spirometer slowly until the lungs are cleared of air. SVC is measured in liters (L). The greater the mean change from baseline to 6 months, the worse the outcome. For example, -10 is worse than -6.
measure: Muscle Strength
time frame: 6 months
description: Muscle strength measured by manual muscle testing (MMT) and instrumented hand-held dynamometry. Maximum muscle strength is assessed by measuring the best of 2 handgrips represented as kilograms (kg). The greater the change from baseline to month 6, the worse off the subject is. For example, a change of -0.50 is worse than -0.40.
measure: Use of Non-invasive Ventilation
time frame: 6 months
description: Non-invasive ventilation (NIV) utilization measured by clinically indicated prescription for NIV intervention and time to clinically indicated prescription for NIV intervention in each group (for early ALS subjects only). This is intended to count the number of subjects who had to go on non-invasive ventilation, as prescribed by the Principal Investigator, during study participation.
measure: The Mean Change in Baseline to Month 6 in Quality of Life as Measured by the Amyotrophic Lateral Sclerosis Assessment Questionnaire - 5
time frame: 6 months
description: A patient self-reported questionnaire specifically designed to measure 5 areas of health: physical mobility, activities of daily living and independence, eating and drinking, communication, and emotional functioning. The ALSAQ-5 is brief and easy to complete questionnaire and has undergone rigorous testing for validity, reliability, and sensitivity to change and has been shown to be a robust tool for assessing ALS. The lowest possible score is 0 and the highest possible score is 20. The greater the mean decrease from baseline to Month 6, the group was considered worse off. For example, -2 is worse than -1. The greater the mean increase from baseline to Month 6, the group was considered improved. For example, 2 is better than 1.
measure: Clinical Global Impression of Change (CGIC)
time frame: 6 months
description: A scale used to provide a global rating of illness severity, improvement, and response to treatment. It is a 3-item observer rating scale and uses a 7-point rating scale. The scale was rated relative to the previous standard of care visit prior to randomization for entry, i.e., -3 much much much worse, -2 much much worse, - 1 much worse, 0 no change, +1 much better, +2 much much better, +3 much, much, much better. Ratings were provided by the Investigator. The greater the mean decrease from baseline to Month 6, the group was considered worse off. For example, -2 is worse than -1. The greater the mean increase from baseline to Month 6, the group was considered improved. For example, 2 is better than 1.
arm group label: Placebo (for MN-166)
arm group type: Placebo Comparator
description: Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.
arm group label: MN-166
arm group type: Experimental
description: MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months.
intervention type: Drug
intervention name: Placebo (for MN-166)
arm group label: Placebo (for MN-166)
other name: Sugar pill manufactured to mimic MN-166 10 mg tablet
intervention type: Drug
intervention name: MN-166
arm group label: MN-166
other name: ibudilast
intervention type: Drug
intervention name: riluzole
description: Patient is given 50 mg riluzole twice daily.
arm group label: MN-166
arm group label: Placebo (for MN-166)
other name: Rilutek
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Benjamin R Brooks, M.D.
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
facility: 
country: United States
url: http://carolinashealthcare.org
description: Please call 1-844-CMC-ALS1 (1-844-262-2571) toll free for information on this trial.
responsible party type: Sponsor
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
mesh term: Sclerosis
mesh term: Ibudilast
mesh term: Riluzole
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 