<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/NCT03834766</url>
  </required_header>
  <id_info>
    <org_study_id>TRI108-ADD-400</org_study_id>
    <nct_id>NCT03834766</nct_id>
  </id_info>
  <brief_title>Amphetamine Extended-Release Tablets in the Treatment of Adults With ADHD</brief_title>
  <official_title>Amphetamine Extended-Release Tablets in the Treatment of Adults With ADHD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tris Pharma, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Premier Research Group plc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Tris Pharma, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the efficacy of AMPH ER TAB compared to placebo in adult patients with ADHD aged&#xD;
      18 to 60 years.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind (DB), placebo-controlled, parallel, study to assess the&#xD;
      efficacy and safety of AMPH ER TAB compared to placebo for the treatment of ADHD in adults&#xD;
      aged 18 to 60 years.&#xD;
&#xD;
      After Screening and Baseline evaluations are complete, eligible subjects will be randomized&#xD;
      in the study to take DB AMPH ER TAB or matching placebo orally once daily in the morning&#xD;
      beginning the day after the Baseline visit for 5 weeks. Dose will be titrated on a weekly&#xD;
      basis to reach 20 mg per day.Subjects who cannot tolerate the study drug will be discontinued&#xD;
      from the study.&#xD;
&#xD;
      A Math Test placement test will be done at Screening or at Baseline. At Visit 5, efficacy&#xD;
      assessments will include the administration of serial Math Tests at pre-dose and at 0.5, 1,&#xD;
      2, 4, 8, 10, 12, 13, and 14 hours post-dose.&#xD;
&#xD;
      Adult Investigator Symptom Rating Scale (AISRS) and Clinical Global Impression Scale Severity&#xD;
      (CGI-S) will be conducted at Baseline and Visits 1 to 5. Digit Symbol Substitution Test&#xD;
      (DSST) will be administered at Baseline and Visit 5.&#xD;
&#xD;
      Safety assessments will include treatment-emergent adverse events, physical examination,&#xD;
      vital signs, body weight, Columbia Suicide Severity Rating Scale (C-SSRS), and direct&#xD;
      questioning to assess for sleep, appetite, mood and psychotic events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 6, 2019</start_date>
  <completion_date type="Actual">October 19, 2019</completion_date>
  <primary_completion_date type="Actual">October 19, 2019</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>This is a randomized, double-blind (DB), placebo-controlled, parallel study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>AMPH ER Tab 5, 10, 15 &amp; 20 mg Vs. Matching Placebo</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Math Test score over all post-dose time points assessed during the administration of serial Math Tests at Visit 5</measure>
    <time_frame>6 monts</time_frame>
    <description>The primary efficacy endpoint will be assessed using a linear Mixed Model Repeated Measures (MMRM) analysis using SAS® PROC MIXED. The model will include treatment, time and treatment by time as fixed effects and subject as a random effect. Pre-dose Math Test score will be included as a covariate. The difference between AMPH ER TAB and placebo will be assessed at the alpha = 0.05 level of significance.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Onset of clinical effect</measure>
    <time_frame>6 months</time_frame>
    <description>Defined as the first time point post-dose when treatment effect of AMPH ER TAB versus placebo, evaluated using Math Test scores (attempted + correct) is significant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of clinical effect</measure>
    <time_frame>6 months</time_frame>
    <description>Defined as the time between last time point to the first time point post-dose with significant treatment effect of AMPH ER TAB versus placebo evaluated using Math Test scores (attempted + correct).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">130</enrollment>
  <condition>ADHD</condition>
  <arm_group>
    <arm_group_label>AMPH ER Tab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Amphetamine Extended Release Tablets 5, 10, 15 and 20 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Matching Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching Placebo Tablets 5, 10, 15 and 20 mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AMPH ER Tab 5, 10, 15 and 20 mg</intervention_name>
    <description>Amphetamine</description>
    <arm_group_label>AMPH ER Tab</arm_group_label>
    <other_name>Amphetamine Extended Release Tablets</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AMPH ER Tab Matching Placebo 5, 10, 15 and 20 mg</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Matching Placebo</arm_group_label>
    <other_name>Amphetamine Extended Release Tablets Matching Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Male or female aged 18 to 60 years, inclusive at the time of Screening.&#xD;
&#xD;
          2. Diagnosed with ADHD using the DSM-5 criteria based on the Adults ADHD Clinical&#xD;
             Diagnostic Scale (ACDS).&#xD;
&#xD;
          3. IQ within normal range based upon clinical opinion of the Investigator.&#xD;
&#xD;
          4. Baseline AISRS total score greater than or equal to 26.&#xD;
&#xD;
          5. Baseline score of 4 or higher in CGI-S.&#xD;
&#xD;
          6. Females who participate in this study will be of childbearing or non-childbearing&#xD;
             potential:&#xD;
&#xD;
               -  Childbearing potential: Physically capable of becoming pregnant&#xD;
&#xD;
               -  Non-childbearing potential:&#xD;
&#xD;
                    -  Permanently sterile (i.e., both ovaries removed, uterus removed, or&#xD;
                       bilateral tubal ligation for at least 6 weeks or documented successful&#xD;
                       hysteroscopic sterilization); and/or&#xD;
&#xD;
                    -  Post-menopausal (no menstrual period for at least 12 consecutive months&#xD;
                       without any other medical cause).&#xD;
&#xD;
          7. Females of childbearing potential must be non-lactating and must have a negative serum&#xD;
             pregnancy test at Screening.&#xD;
&#xD;
          8. Willing to use acceptable, effective methods of contraception.&#xD;
&#xD;
          9. Be able to attend the clinic regularly and reliably.&#xD;
&#xD;
         10. Be able to understand, read, write, and speak English fluently to complete the study&#xD;
             related materials.&#xD;
&#xD;
         11. Be informed of the nature of the study and give written consent prior to any study&#xD;
             procedure.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current or lifetime history of bipolar disorder or any psychotic disorder as&#xD;
             established by Mini International Neuropsychiatric Interview (M.I.N.I.) 7.0.2.&#xD;
&#xD;
          2. Current history of major depression, generalized anxiety disorder,&#xD;
             obsessive-compulsive disorder, panic disorder, or post-traumatic stress disorder as&#xD;
             established by the M.I.N.I. 7.0.2.&#xD;
&#xD;
          3. Known history of chronic medical illnesses including untreated thyroid disease,&#xD;
             peripheral vasculopathy, known structural cardiac disorders, serious cardiac&#xD;
             conditions, serious arrhythmias, cardiomyopathy, and known family history of sudden&#xD;
             death.&#xD;
&#xD;
          4. History of uncontrolled hypertension or a resting systolic blood pressure &gt;140 mmHg or&#xD;
             diastolic blood pressure &gt;90 mmHg. Subjects with well-controlled hypertension on a&#xD;
             stable dose for at least 3 months of anti-hypertensives will be allowed to&#xD;
             participate.&#xD;
&#xD;
          5. Have clinically significant findings in vital signs measurements at Screening&#xD;
             including:&#xD;
&#xD;
               -  Systolic blood pressure &gt;140 mmHg or diastolic blood pressure &gt;90 mmHg&#xD;
&#xD;
               -  Heart rate &gt;100 bpm&#xD;
&#xD;
          6. Known history or presence of significant renal or hepatic disease, as indicated by&#xD;
             clinical laboratory assessment:&#xD;
&#xD;
               -  Liver function test results ≥2 times the upper normal limit&#xD;
&#xD;
               -  Abnormal blood urea nitrogen, or creatinine levels&#xD;
&#xD;
          7. Clinically significant abnormal electrocardiogram or cardiac findings on physical&#xD;
             examination (including the presence of a pathologic murmur).&#xD;
&#xD;
          8. Use of the following medications within 14 days of Baseline Visit:&#xD;
&#xD;
               -  Atomoxetine&#xD;
&#xD;
               -  Monoamine oxidase inhibitors (e.g., selegiline, isocarboxazid, phenelzine,&#xD;
                  tranylcypromine)&#xD;
&#xD;
               -  Tricyclic antidepressants (e.g., desipramine, protriptyline).&#xD;
&#xD;
          9. Use of the following medications within 3 days of Baseline Visit:&#xD;
&#xD;
               -  Gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid&#xD;
                  hydrochloride [HCl], ascorbic acid)&#xD;
&#xD;
               -  Urinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate,&#xD;
                  methenamine salts).&#xD;
&#xD;
         10. Use of fluoxetine within 30 days of Baseline Visit.&#xD;
&#xD;
         11. Use of stimulant medications within 1 week of Baseline Visit.&#xD;
&#xD;
         12. Planned use of prohibited drugs or agents from the Screening visit through the end of&#xD;
             the study.&#xD;
&#xD;
         13. Participation in a clinical study in which an investigational drug was administered&#xD;
             within 30 days prior to Screening.&#xD;
&#xD;
         14. Abnormal clinically significant laboratory test values at Screening that, in the&#xD;
             opinion of the Medical Monitor or Sponsor, would preclude study participation.&#xD;
&#xD;
         15. Known history of allergy/hypersensitivity to amphetamine or any of the components of&#xD;
             AMPH ER TAB.&#xD;
&#xD;
         16. Known history of lack of clinical response to amphetamine based upon Investigator&#xD;
             judgment.&#xD;
&#xD;
         17. Positive test result for HIV, Hepatitis B surface antigen, or Hepatitis C antibody.&#xD;
&#xD;
         18. Any uncontrolled medical condition that, in the opinion of Medical Monitor or Sponsor,&#xD;
             would preclude study participation.&#xD;
&#xD;
         19. History or presence of alcohol dependence or substance abuse disorder according to&#xD;
             DSM-5 or within the last 12 months.&#xD;
&#xD;
         20. Subject's inability or unwillingness to follow directions from the study research&#xD;
             staff.&#xD;
&#xD;
         21. Answer of &quot;yes&quot; to questions 4 or 5 of the C-SSRS within the last 2 years.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew J. Cutler, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Meridien Research Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Meridien Research</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>344201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meridien Research, Inc.</name>
      <address>
        <city>Maitland</city>
        <state>Florida</state>
        <zip>32751</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Psychiatry and Behavioral Medicine</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>February 4, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>December 5, 2019</last_update_submitted>
  <last_update_submitted_qc>December 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amphetamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>October 19, 2021</submitted>
    <returned>November 17, 2021</returned>
    <submitted>June 22, 2023</submitted>
    <returned>July 12, 2023</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03834766
org study id: TRI108-ADD-400
nct id: NCT03834766
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
To evaluate the efficacy of AMPH ER TAB compared to placebo in adult patients with ADHD aged
      18 to 60 years.
This is a randomized, double-blind (DB), placebo-controlled, parallel, study to assess the
      efficacy and safety of AMPH ER TAB compared to placebo for the treatment of ADHD in adults
      aged 18 to 60 years.

      After Screening and Baseline evaluations are complete, eligible subjects will be randomized
      in the study to take DB AMPH ER TAB or matching placebo orally once daily in the morning
      beginning the day after the Baseline visit for 5 weeks. Dose will be titrated on a weekly
      basis to reach 20 mg per day.Subjects who cannot tolerate the study drug will be discontinued
      from the study.

      A Math Test placement test will be done at Screening or at Baseline. At Visit 5, efficacy
      assessments will include the administration of serial Math Tests at pre-dose and at 0.5, 1,
      2, 4, 8, 10, 12, 13, and 14 hours post-dose.

      Adult Investigator Symptom Rating Scale (AISRS) and Clinical Global Impression Scale Severity
      (CGI-S) will be conducted at Baseline and Visits 1 to 5. Digit Symbol Substitution Test
      (DSST) will be administered at Baseline and Visit 5.

      Safety assessments will include treatment-emergent adverse events, physical examination,
      vital signs, body weight, Columbia Suicide Severity Rating Scale (C-SSRS), and direct
      questioning to assess for sleep, appetite, mood and psychotic events.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a randomized, double-blind (DB), placebo-controlled, parallel study
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: AMPH ER Tab 5, 10, 15 & 20 mg Vs. Matching Placebo
measure: Math Test score over all post-dose time points assessed during the administration of serial Math Tests at Visit 5
time frame: 6 monts
description: The primary efficacy endpoint will be assessed using a linear Mixed Model Repeated Measures (MMRM) analysis using SAS® PROC MIXED. The model will include treatment, time and treatment by time as fixed effects and subject as a random effect. Pre-dose Math Test score will be included as a covariate. The difference between AMPH ER TAB and placebo will be assessed at the alpha = 0.05 level of significance.
measure: Onset of clinical effect
time frame: 6 months
description: Defined as the first time point post-dose when treatment effect of AMPH ER TAB versus placebo, evaluated using Math Test scores (attempted + correct) is significant.
measure: Duration of clinical effect
time frame: 6 months
description: Defined as the time between last time point to the first time point post-dose with significant treatment effect of AMPH ER TAB versus placebo evaluated using Math Test scores (attempted + correct).
arm group label: AMPH ER Tab
arm group type: Active Comparator
description: Amphetamine Extended Release Tablets 5, 10, 15 and 20 mg
arm group label: Matching Placebo
arm group type: Placebo Comparator
description: Matching Placebo Tablets 5, 10, 15 and 20 mg
intervention type: Drug
intervention name: AMPH ER Tab 5, 10, 15 and 20 mg
description: Amphetamine
arm group label: AMPH ER Tab
other name: Amphetamine Extended Release Tablets
intervention type: Drug
intervention name: AMPH ER Tab Matching Placebo 5, 10, 15 and 20 mg
description: Placebo
arm group label: Matching Placebo
other name: Amphetamine Extended Release Tablets Matching Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Andrew J. Cutler, MD
role: Principal Investigator
affiliation: Meridien Research Inc.
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Amphetamine
sharing ipd: No
submitted: October 19, 2021
returned: November 17, 2021
submitted: June 22, 2023
returned: July 12, 2023