xml: <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/NCT06042257</url>
    </required_header>
    <id_info>
      <org_study_id>Pro00111256</org_study_id>
      <secondary_id>HHSN275201800003I</secondary_id>
      <nct_id>NCT06042257</nct_id>
    </id_info>
    <brief_title>Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS)</brief_title>
    <acronym>HYP01</acronym>
    <official_title>Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Rachel G. Greenberg, MD, MB, MHS</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>The Emmes Company, LLC</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>Duke University</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to determine efficacy of guanfacine immediate release (GIR) for&#xD;
        the treatment of hyperactivity/impulsivity and inattention in children 6-12 years of age with&#xD;
        Down syndrome (DS) after 8 weeks of treatment.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a randomized, double-blind, placebo-controlled flexibly dosed trial of guanfacine&#xD;
        immediate release (GIR) in children with Down syndrome (DS) and symptoms of hyperactivity,&#xD;
        inattention, and impulsivity. Participants will undergo a screening period of up to 29 days.&#xD;
        Eligible participants meeting study criteria will be randomized 2:1 GIR or placebo. There are&#xD;
        a total of up to 4 in person visits (screening, baseline, at Week 4, and at Week 8).&#xD;
        Participants will receive GIR or placebo for up to 8 weeks. Weekly dose escalation will be&#xD;
        determined via a telephone assessment at Weeks 1-3 and Weeks 4-7. Unmasking of participant&#xD;
        and site staff will occur at the week 8, in-person visit. After unmasking, participants who&#xD;
        were randomized to receive GIR will be given the option to 1) remain on GIR and to transition&#xD;
        to open-label GIR per standard of care or 2) taper off of GIR. A Telephone Safety Assessment&#xD;
        will be conducted for all participants, at 5 (+2) days after final study product&#xD;
        administration. Blood specimens will be collected at the Week 4 and Week 8 visits for&#xD;
        Pharmacokinetic (PK) analyses and lab assessments. Participants will be asked to keep a daily&#xD;
        study drug diary and will complete study measures at screening/baseline, Week 4 and Week 8.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 2023</start_date>
    <completion_date type="Anticipated">February 2026</completion_date>
    <primary_completion_date type="Anticipated">November 2025</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>
      <intervention_model_description>Participants will be randomized 2:1 to GIR or placebo.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
      <masking_description>A masked investigational pharmacist or designee will dispense study product according to randomization treatment assignments. All other site staff as well as participants and parents/legal guardians will also be masked for up to 8 weeks while the study participant is receiving study product.&#xD;
  Participants, parents/legal guardians, site staff, and study administrators will be unmasked at the 8 week study visit.&#xD;
  Emergency unmasking may occur at any time throughout the study in the event that knowledge of the actual treatment is absolutely essential for further management of the participant.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core</measure>
      <time_frame>Baseline to Week 8</time_frame>
      <description>Change from baseline to Week 8 of the ABC-H subscale score. The ABC-H is a subscale of the ABC. Each of the 16 items is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score range is 0 to 48, where a higher score indicates endorsement of greater hyperactivity. Rating based on patient's behavior in last 4 weeks.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core</measure>
      <time_frame>Baseline to Week 4</time_frame>
      <description>Change from baseline to Week 4 of the ABC-H subscale score. The ABC-H is a subscale of the ABC. Each of the 16 items is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score range is 0 to 48, where a higher score indicates endorsement of greater hyperactivity. Rating based on patient's behavior in last 4 weeks.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants with a CGI-I score of 2 or better at Week 4</measure>
      <time_frame>Baseline to Week 4</time_frame>
      <description>CGI-I specific to hyperactivity, inattention and impulsivity behaviors. The CGI-I is a seven-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants with a CGI-I score of 2 or better at Week 8</measure>
      <time_frame>Baseline to Week 8</time_frame>
      <description>CGI-I specific to hyperactivity, inattention and impulsivity behaviors. The CGI-I is a seven-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety of GIR (guanfacine immediate release)</measure>
      <time_frame>Baseline through Week 8</time_frame>
      <description>Number of participants with adverse events (AEs), serious adverse events (SAEs), or events of special interest (ESIs).</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Hyperactivity in Children With Down Syndrome</condition>
    <condition>Impulsivity in Children With Down Syndrome</condition>
    <arm_group>
      <arm_group_label>Guanfacine Hydrochloride Immediate Release</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Eligible participants will receive GIR for up to 8 weeks. The treatment period will consist of study product administration from day 0 through day 56 with a masked dose-escalation period from day 0 through day 49.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Eligible participants will receive Placebo for up to 8 weeks.The treatment period will consist of study product administration from day 0 through day 56 with a masked dose-escalation period from day 0 through day 49.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Guanfacine Hydrochloride Immediate Release</intervention_name>
      <description>0.5 mg capsules</description>
      <arm_group_label>Guanfacine Hydrochloride Immediate Release</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Matching placebo capsule</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion:&#xD;
  &#xD;
            1. Parent/Legal Guardian can understand the consent process and is willing to provide&#xD;
               informed consent/HIPAA authorization prior to the conduct of any study-related&#xD;
               procedures. When applicable, the minor participant is willing to provide assent.&#xD;
  &#xD;
            2. Participant has clinical diagnosis of non-mosaic DS.&#xD;
  &#xD;
            3. Participant is between 6 and 12 years of age (inclusive) at time of consent.&#xD;
  &#xD;
            4. Participant weight is ≥ 25 kg.&#xD;
  &#xD;
            5. Participant has clinically significant symptoms of hyperactivity, inattention and&#xD;
               impulsivity manifested as minimum scores of the following rating scales within 30 days&#xD;
               of randomization:&#xD;
  &#xD;
                 1. A minimum score of 18 on the parent-reported ABC-H subscale, AND&#xD;
  &#xD;
                 2. A minimum score of moderate or greater (≥ 4) on the clinician reported Clinical&#xD;
                    Global Impression Severity (CGI-S) score specific to hyperactivity, inattention&#xD;
                    and impulsivity behaviors.&#xD;
  &#xD;
            6. Participant has co-morbid medical screening and clearance to proceed with a&#xD;
               non-stimulant medication trial with GIR within 30 days of randomization.&#xD;
  &#xD;
            7. Participant is willing and able to comply with study procedures, including adherence&#xD;
               to medication dosing schedule.&#xD;
  &#xD;
          Exclusion:&#xD;
  &#xD;
            1. Participant has received guanfacine (any formulation) within 30 days of randomization.&#xD;
  &#xD;
            2. Participant has received any of the following concomitant medication classes within 30&#xD;
               days of randomization:&#xD;
  &#xD;
                 1. Strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan,&#xD;
                    grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir,&#xD;
                    mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir,&#xD;
                    telaprevir, telithromycin, and voriconazole)&#xD;
  &#xD;
                 2. Strong CYP3A4 inducers (e.g., avasimibe, carbamazepine, phenytoin, rifampin, and&#xD;
                    St. John's wort)&#xD;
  &#xD;
            3. Participant has a psychiatric comorbidity, such as major depressive disorder, bipolar&#xD;
               disorder, obsessive-compulsive disorder, or a psychotic disorder, that requires a&#xD;
               pharmacological treatment other than guanfacine&#xD;
  &#xD;
            4. For participants ≥ 8 years old at the time of consent, participant has a history of&#xD;
               suicidality or positive screen on Ask Suicide-Screening Questions (asQ) Tool.&#xD;
  &#xD;
            5. Participant is currently in or plans to participate in another interventional study.&#xD;
  &#xD;
            6. Participant has a known hypersensitivity to guanfacine.&#xD;
  &#xD;
            7. Participant has had a previous guanfacine treatment failure, as determined by their&#xD;
               primary treating physician.&#xD;
  &#xD;
            8. Participant has had a seizure within the last 6 months.&#xD;
  &#xD;
            9. Participant has had a change in their anti-convulsant dose within the last 4 weeks.&#xD;
  &#xD;
           10. Participant has a cardiac-related condition including:&#xD;
  &#xD;
                 1. Significant symptomatic bradycardia;&#xD;
  &#xD;
                 2. 2nd degree or 3rd degree (complete) heart block;&#xD;
  &#xD;
                 3. Baseline heart rate (HR) or systolic blood pressure (BP) &gt; 2 standard deviations&#xD;
                    (SD) below mean for age as determined by medical examination;&#xD;
  &#xD;
                 4. History of aborted sudden cardiac death, unexplained syncope or near syncope, or&#xD;
                    historical use of a pacemaker as determined by medical history will require&#xD;
                    clearance by cardiology prior to enrollment;&#xD;
  &#xD;
                 5. Known history of congenital heart disease which requires ongoing care for&#xD;
                    monitoring or management will require clearance by cardiology prior to&#xD;
                    enrollment.&#xD;
  &#xD;
           11. Participant has a history of untreated severe obstructive sleep apnea defined as&#xD;
               obstructive apnea hypopnea index (OAHI) ≥ 10 events per hour or aortic regurgitation&#xD;
               (AR). Participants with an OAHI index &gt; 10/hr are eligible if managed with continuous&#xD;
               positive airway pressure (CPAP).&#xD;
  &#xD;
           12. Participant has untreated thyroid disease.&#xD;
  &#xD;
           13. Participant has a known hepatic impairment defined as aspartate aminotransferase (AST)&#xD;
               or alanine aminotransferase (ALT) &gt; 2x the upper limit of normal (ULN) for age.&#xD;
  &#xD;
           14. Participant has known impending or renal failure defined as:&#xD;
  &#xD;
                 1. Anuria diagnosed within 12 hours prior to enrollment;&#xD;
  &#xD;
                 2. Requiring renal replacement therapy.&#xD;
  &#xD;
           15. Participant is pregnant.&#xD;
  &#xD;
           16. Participant has any condition which would make the participant, in the opinion of the&#xD;
               investigator, unsuitable for the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>6 Years</minimum_age>
      <maximum_age>12 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Rachel Greenberg</last_name>
      <role>Principal Investigator</role>
      <affiliation>DCRI</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Elena Soler</last_name>
      <phone>919- 668-8503</phone>
      <email>elena.soler@duke.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Zoe Sund</last_name>
      <phone>202-573-2673</phone>
      <email>zoe.sund@duke.edu</email>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Duke University</investigator_affiliation>
      <investigator_full_name>Rachel G. Greenberg, MD, MB, MHS</investigator_full_name>
      <investigator_title>Associate Professor of Pediatrics</investigator_title>
    </responsible_party>
    <keyword>hyperactivity</keyword>
    <keyword>impulsivity</keyword>
    <keyword>inattention</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Hyperkinesis</mesh_term>
      <mesh_term>Down Syndrome</mesh_term>
      <mesh_term>Syndrome</mesh_term>
      <mesh_term>Impulsive Behavior</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Guanfacine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06042257
  org study id: Pro00111256
  secondary id: HHSN275201800003I
  nct id: NCT06042257
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The purpose of this study is to determine efficacy of guanfacine immediate release (GIR) for
        the treatment of hyperactivity/impulsivity and inattention in children 6-12 years of age with
        Down syndrome (DS) after 8 weeks of treatment.
  This is a randomized, double-blind, placebo-controlled flexibly dosed trial of guanfacine
        immediate release (GIR) in children with Down syndrome (DS) and symptoms of hyperactivity,
        inattention, and impulsivity. Participants will undergo a screening period of up to 29 days.
        Eligible participants meeting study criteria will be randomized 2:1 GIR or placebo. There are
        a total of up to 4 in person visits (screening, baseline, at Week 4, and at Week 8).
        Participants will receive GIR or placebo for up to 8 weeks. Weekly dose escalation will be
        determined via a telephone assessment at Weeks 1-3 and Weeks 4-7. Unmasking of participant
        and site staff will occur at the week 8, in-person visit. After unmasking, participants who
        were randomized to receive GIR will be given the option to 1) remain on GIR and to transition
        to open-label GIR per standard of care or 2) taper off of GIR. A Telephone Safety Assessment
        will be conducted for all participants, at 5 (+2) days after final study product
        administration. Blood specimens will be collected at the Week 4 and Week 8 visits for
        Pharmacokinetic (PK) analyses and lab assessments. Participants will be asked to keep a daily
        study drug diary and will complete study measures at screening/baseline, Week 4 and Week 8.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Participants will be randomized 2:1 to GIR or placebo.
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  masking description: A masked investigational pharmacist or designee will dispense study product according to randomization treatment assignments. All other site staff as well as participants and parents/legal guardians will also be masked for up to 8 weeks while the study participant is receiving study product.
  Participants, parents/legal guardians, site staff, and study administrators will be unmasked at the 8 week study visit.
  Emergency unmasking may occur at any time throughout the study in the event that knowledge of the actual treatment is absolutely essential for further management of the participant.
  measure: Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core
  time frame: Baseline to Week 8
  description: Change from baseline to Week 8 of the ABC-H subscale score. The ABC-H is a subscale of the ABC. Each of the 16 items is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score range is 0 to 48, where a higher score indicates endorsement of greater hyperactivity. Rating based on patient's behavior in last 4 weeks.
  measure: Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core
  time frame: Baseline to Week 4
  description: Change from baseline to Week 4 of the ABC-H subscale score. The ABC-H is a subscale of the ABC. Each of the 16 items is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score range is 0 to 48, where a higher score indicates endorsement of greater hyperactivity. Rating based on patient's behavior in last 4 weeks.
  measure: Proportion of participants with a CGI-I score of 2 or better at Week 4
  time frame: Baseline to Week 4
  description: CGI-I specific to hyperactivity, inattention and impulsivity behaviors. The CGI-I is a seven-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse.
  measure: Proportion of participants with a CGI-I score of 2 or better at Week 8
  time frame: Baseline to Week 8
  description: CGI-I specific to hyperactivity, inattention and impulsivity behaviors. The CGI-I is a seven-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse.
  measure: Safety of GIR (guanfacine immediate release)
  time frame: Baseline through Week 8
  description: Number of participants with adverse events (AEs), serious adverse events (SAEs), or events of special interest (ESIs).
  arm group label: Guanfacine Hydrochloride Immediate Release
  arm group type: Active Comparator
  description: Eligible participants will receive GIR for up to 8 weeks. The treatment period will consist of study product administration from day 0 through day 56 with a masked dose-escalation period from day 0 through day 49.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Eligible participants will receive Placebo for up to 8 weeks.The treatment period will consist of study product administration from day 0 through day 56 with a masked dose-escalation period from day 0 through day 49.
  intervention type: Drug
  intervention name: Guanfacine Hydrochloride Immediate Release
  description: 0.5 mg capsules
  arm group label: Guanfacine Hydrochloride Immediate Release
  intervention type: Drug
  intervention name: Placebo
  description: Matching placebo capsule
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 6 Years
  maximum age: 12 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Rachel Greenberg
  role: Principal Investigator
  affiliation: DCRI
  last name: Elena Soler
  phone: 919- 668-8503
  email: elena.soler@duke.edu
  last name: Zoe Sund
  phone: 202-573-2673
  email: zoe.sund@duke.edu
  responsible party type: Sponsor-Investigator
  investigator affiliation: Duke University
  investigator full name: Rachel G. Greenberg, MD, MB, MHS
  investigator title: Associate Professor of Pediatrics
  mesh term: Hyperkinesis
  mesh term: Down Syndrome
  mesh term: Syndrome
  mesh term: Impulsive Behavior
  mesh term: Guanfacine
  sharing ipd: No