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/NCT06014424</url>
    </required_header>
    <id_info>
      <org_study_id>3878</org_study_id>
      <nct_id>NCT06014424</nct_id>
    </id_info>
    <brief_title>Cannabinoid Liquid Medication Intervention Trial</brief_title>
    <acronym>CALM-IT</acronym>
    <official_title>Cannabinoid Liquid Medication Intervention Trial (CALM-IT)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sunnybrook Health Sciences Centre</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sunnybrook Health Sciences Centre</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        CALM-IT is a Randomized, double-blind, placebo-controlled cross-over clinical trial. Safety&#xD;
        and efficacy of JZP541 assessed for managing agitation in patients with AD and to identify&#xD;
        novel biomarkers of agitation severity and treatment response.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study will look at whether JZP541 is an effective treatment for agitation in Alzheimer's&#xD;
        disease (AD). JZP541 is a botanical cannabinoid drug product containing cannabidiol (CBD),&#xD;
        cannabichrome (CBC) and delta-9-tetrahydrocannabinol (THC), amongst other cannabinoid and&#xD;
        noncannabinoid plant-derived components. Cannabis products are legal for purchase in Canada.&#xD;
  &#xD;
        Agitation is common in AD and is known to correlate with physical health problems such as&#xD;
        falls and weight loss, AD progression, and caregiver burden. Current treatments for agitation&#xD;
        in AD are not beneficial for everyone and there are concerns regarding their safety. Treating&#xD;
        agitation is important in improving the quality of life of AD patients and their families and&#xD;
        there is a need to identify safer and more effective treatments for agitation in AD.&#xD;
  &#xD;
        The structure of this trial is called a &quot;cross-over study&quot;. Participants will be randomized&#xD;
        to receive either JZP541 or placebo during the first of two treatment phases. They will then&#xD;
        cross-over to the opposite treatment during the second treatment phase. Participants will be&#xD;
        on the study treatment for a total of 19 weeks and then will be followed for 4 more weeks&#xD;
        after finishing the study treatment. There will be 12 study visits approximately every 2&#xD;
        weeks and 8 telephone visits every week during the study.&#xD;
  &#xD;
        In addition to looking at the effectiveness of JZP541 in treating agitation, the researchers&#xD;
        will also look at whether it is beneficial for other relevant outcomes for patients with AD&#xD;
        including overall neuropsychiatric symptoms, caregiver distress, cognition, nutritional&#xD;
        status, and pain.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 20, 2023</start_date>
    <completion_date type="Anticipated">December 29, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 29, 2026</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
      <masking_description>This is a double-blind study. Participants, Subsequent decision maker and investigator will be blinded to the treatment arm. Unblinding will not be allowed unless there are exceptional clinical circumstances that justify it</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Agitation - Cohen-Mansfield Agitation Inventory (CMAI)</measure>
      <time_frame>Baseline (0 Weeks) to 22 Weeks</time_frame>
      <description>A 29-point scale that measures agitation in two dimensions, verbal and physical, each of which having two poles, aggressive and on-aggressive. Scores range from 29-203 points, with a higher score indicating a worse outcome.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Behaviour - Neuropsychiatric Inventory - Clinician Scale (NPI-C)</measure>
      <time_frame>Baseline (0 Weeks) to 22 Weeks</time_frame>
      <description>A widely used assessment of behaviour disturbances in dementia, including: apathy agitation, delusions, hallucinations, depression, euphoria, abeerant motor behaviour, irritability, disinhibition, anxiety, sleeping, and eating. The frequency and severity of these symptoms are judged on a 4-point and 3-point scale, respectively. Scores range from 0-144 points, with a higher score indicating a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cognition - Standardized Mini-Mental State Examination (sMMSE)</measure>
      <time_frame>Baseline (0 Weeks) to 22 Weeks</time_frame>
      <description>Measures global cognition, and assesses orientation to time and place, immediate recall, short-term verbal memory, calculation, language, and construct ability. Scores range from 0-30 points, with a lower score indicating a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Weight</measure>
      <time_frame>Baseline (0 Weeks) to 22 Weeks</time_frame>
      <description>Weight will be collected in kilograms. A change of 7% in weight will be considered clinically significant change.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Nutritional Status - Mini Nutritional Assessment - Short Form (MNA-SF)</measure>
      <time_frame>Baseline (0 Weeks) to 22 Weeks</time_frame>
      <description>A structured interview consisting of 6 items that categorizes patients as malnourished, at risk of malnutrition, or of normal nutritional status. Scores range from 0-14 points, with a lower score indicating a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pain - Pain Assessment Checklist for Seniors with Limited Ability to Communicate - II (PACSLAC-II)</measure>
      <time_frame>Baseline (0 Weeks) to 22 Weeks</time_frame>
      <description>A 31-item observer-rated scale assessing facial expressions, activity/body movements, social/personality/mood indicators and mental status changes. Scores range form 0-31 points, with a higher score indicating a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Global Change - Alzheimer's Disease Cooperative Study - Clinical Global Impression of Severity/Change (ADCS-CGIS/C)</measure>
      <time_frame>Baseline (0 Weeks) to 22 Weeks</time_frame>
      <description>A commonly-used clinician-rated scale that quantifies disease severity and clinical change (worsening, no change, or improvement), based on information regarding the patient's medical history, cognition, behaviour, and function. Scores range from 1-7, with a lower score indicating a worse outcome.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Sedation - Udvalg for Kliniske Undersøgelser (UKU) Side-Effect Rating Scale</measure>
      <time_frame>Baseline (0 Weeks) to 22 Weeks</time_frame>
      <description>Sedation will be measured using the Sleepiness/Sedation subscale of the UKU-Side Effect Rating Scale. The UKU is a clinician-rated scale that assesses the side effects psychopharmacological medications. Scores range from 0-3, with a higher score indicating more sleepiness/sedation.</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Alzheimer Disease</condition>
    <arm_group>
      <arm_group_label>JZP541</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants randomized to the JZP541 arm will be titrated up to a maximum dose of 26 mL/day</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants randomized to the placebo will be titrated up to a maximum dose of 26 mL/day</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>JZP541</intervention_name>
      <description>Participants in this arm will receive ZP541 for 8 weeks during the first treatment period. They will then receive a two-week single-blind placebo washout before moving into the second 8-week treatment period, during which they will receive the opposite study treatment than the one given in the first treatment period.</description>
      <arm_group_label>JZP541</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Participants in this arm will receive placebo for 8 weeks during the first treatment period. They will then receive a two-week single-blind placebo washout before moving into the second 8-week treatment period, during which they will receive the opposite study treatment than the one given in the first treatment period.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Males or females ≥55 years of age; female must be post-menopausal or must agree to&#xD;
               comply with contraception requirements. Males should also abide by contraceptive&#xD;
               requirements when the partner is a woman of childbearing potential. Acceptable methods&#xD;
               of contraception include: combined (estrogen and progestogen containing) hormonal&#xD;
               contraception associated with inhibition of ovulation, which may be oral,&#xD;
               intravaginal, or transdermal; progestogen-only hormonal contraception associated with&#xD;
               inhibition of ovulation, which may be oral, injectable, or implantable; intrauterine&#xD;
               device or intrauterine hormone-releasing system; vasectomy of a female subject's male&#xD;
               partner (with medical assessment and confirmation of vasectomy surgical success);&#xD;
               bilateral tubal occlusion&#xD;
  &#xD;
            2. Diagnostic and Statistical Manual of Mental Disorders-5 (DSM 5) criteria for Major&#xD;
               Neurocognitive Disorder due to possible AD. Patients with Major Neurocognitive&#xD;
               Disorder due to multiple etiologies (AD and vascular) will be included&#xD;
  &#xD;
            3. sMMSE ≤24&#xD;
  &#xD;
            4. Presence of clinically significant agitation based on the IPA definition at both&#xD;
               screening and baseline&#xD;
  &#xD;
            5. If treated with cognitive-enhancing medications (cholinesterase inhibitors and/or&#xD;
               memantine), dosage must be stable for at least 3 months prior to study randomization&#xD;
  &#xD;
            6. Availability of a primary caregiver to accompany the participant to study visits and&#xD;
               to participate in the study. The primary caregiver must be sufficiently proficient in&#xD;
               English to complete the required study assessments, as per investigator judgement and&#xD;
               should spend at least 10 hours a week with the participant&#xD;
  &#xD;
            7. Willing and able to provide informed consent and/or have a Substitute Decision Maker&#xD;
               (SDM) provide informed consent on behalf of the participant&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Change in psychotropic medications less than the duration of 5 half-lives of the&#xD;
               medication in question prior to screening (e.g., concomitant antidepressants or&#xD;
               atypical antipsychotics) and any changes during study participation&#xD;
  &#xD;
            2. Administration of strong inducers of CYP3A4 ≤ 14 days prior to first doses of study&#xD;
               intervention or have ongoing requirements for these medications&#xD;
  &#xD;
          3) Use of anticonvulsant medications&#xD;
  &#xD;
          4) Contraindications to CBs, e.g. allergies to cannabis and cannabis products, potential&#xD;
          clinically important drug-drug interactions&#xD;
  &#xD;
          5) Any type of arterial vascular disease, cerebrovascular disease and current uncontrolled&#xD;
          cardiovascular disease (e.g. uncontrolled hypertension, ischemic heart disease, arrhythmia&#xD;
          and severe heart failure), as per investigator assessment&#xD;
  &#xD;
          6) Patients with Cardiovascular Accident in the 3 months prior to Screening (V1)&#xD;
  &#xD;
          7) Impaired hepatic function, as reflected by serum alanine aminotransferase or aspartate&#xD;
          aminotransferase &gt; 2 × upper limit of normal (ULN), or total bilirubin &gt; 1.5&#xD;
  &#xD;
          × ULN; the Investigator may decide to repeat the assessment to confirm criterion prior to&#xD;
          screen failing the participant&#xD;
  &#xD;
          8) Presence of clinically significant impaired renal function at screening, as evidenced by&#xD;
          an estimated creatinine clearance &lt; 30 mL/min/1.73 m2 (as calculated by the glomerular&#xD;
          filtration rate using the Modification of Diet in Renal Disease study equation)&#xD;
  &#xD;
          9) Presence or history of other psychiatric disorders or neurological conditions (e.g.&#xD;
  &#xD;
          psychotic disorders, schizophrenia, stroke, epilepsy) and known or suspected psychotic&#xD;
          disorder in a first degree relative&#xD;
  &#xD;
          10) Participants currently meeting DSM 5 criteria for Major Depressive Episode&#xD;
  &#xD;
          11) History of suicidal behavior or suicidal ideation of type 4 or 5 on the&#xD;
          Columbia-Suicide Severity Rating Scale (C-SSRS)&#xD;
  &#xD;
          12) Current substance dependence (excluding caffeine and nicotine)&#xD;
  &#xD;
          13) Clinically significant delusions and/or hallucinations (NPI-C delusion/hallucinations&#xD;
          subscore ≥4)&#xD;
  &#xD;
          14) Reported use of marijuana or cannabinoid-based medications, products or supplements&#xD;
          (botanical or synthetic) within 1 week prior to randomization&#xD;
  &#xD;
          15) Systolic blood pressure (SBP) &lt; 90 mmHg or &gt; 150 mmHg or diastolic blood pressure (DBP)&#xD;
          &lt; 50 mmHg or &gt; 105 mmHg at screening or baseline (prior to randomization) or a postural&#xD;
          drop in SBP ≥ 20 mmHg or DBP ≥ 10 mmHg at screening&#xD;
  &#xD;
          16) QT Interval Corrected Using Fridericia's Formula &gt; 450 ms (confirmed by 2 consecutive&#xD;
          electrocardiograms (ECGs) or a history of additional risk factors for Torsades de Pointes&#xD;
          (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>55 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>University of Calgary</name>
        <address>
          <city>Calgary</city>
          <state>Alberta</state>
          <zip>T2N 4N1</zip>
          <country>Canada</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Sunnybrook Health Sciences Centre</name>
        <address>
          <city>Toronto</city>
          <state>Ontario</state>
          <zip>M3H0A7</zip>
          <country>Canada</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Ontario Shores Centre for Mental Health Sciences</name>
        <address>
          <city>Whitby</city>
          <state>Ontario</state>
          <zip>L1N 5S9</zip>
          <country>Canada</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 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 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Alzheimer Disease</mesh_term>
    </condition_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/NCT06014424
  org study id: 3878
  nct id: NCT06014424
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  CALM-IT is a Randomized, double-blind, placebo-controlled cross-over clinical trial. Safety
        and efficacy of JZP541 assessed for managing agitation in patients with AD and to identify
        novel biomarkers of agitation severity and treatment response.
  This study will look at whether JZP541 is an effective treatment for agitation in Alzheimer's
        disease (AD). JZP541 is a botanical cannabinoid drug product containing cannabidiol (CBD),
        cannabichrome (CBC) and delta-9-tetrahydrocannabinol (THC), amongst other cannabinoid and
        noncannabinoid plant-derived components. Cannabis products are legal for purchase in Canada.
  
        Agitation is common in AD and is known to correlate with physical health problems such as
        falls and weight loss, AD progression, and caregiver burden. Current treatments for agitation
        in AD are not beneficial for everyone and there are concerns regarding their safety. Treating
        agitation is important in improving the quality of life of AD patients and their families and
        there is a need to identify safer and more effective treatments for agitation in AD.
  
        The structure of this trial is called a "cross-over study". Participants will be randomized
        to receive either JZP541 or placebo during the first of two treatment phases. They will then
        cross-over to the opposite treatment during the second treatment phase. Participants will be
        on the study treatment for a total of 19 weeks and then will be followed for 4 more weeks
        after finishing the study treatment. There will be 12 study visits approximately every 2
        weeks and 8 telephone visits every week during the study.
  
        In addition to looking at the effectiveness of JZP541 in treating agitation, the researchers
        will also look at whether it is beneficial for other relevant outcomes for patients with AD
        including overall neuropsychiatric symptoms, caregiver distress, cognition, nutritional
        status, and pain.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  masking description: This is a double-blind study. Participants, Subsequent decision maker and investigator will be blinded to the treatment arm. Unblinding will not be allowed unless there are exceptional clinical circumstances that justify it
  measure: Agitation - Cohen-Mansfield Agitation Inventory (CMAI)
  time frame: Baseline (0 Weeks) to 22 Weeks
  description: A 29-point scale that measures agitation in two dimensions, verbal and physical, each of which having two poles, aggressive and on-aggressive. Scores range from 29-203 points, with a higher score indicating a worse outcome.
  measure: Behaviour - Neuropsychiatric Inventory - Clinician Scale (NPI-C)
  time frame: Baseline (0 Weeks) to 22 Weeks
  description: A widely used assessment of behaviour disturbances in dementia, including: apathy agitation, delusions, hallucinations, depression, euphoria, abeerant motor behaviour, irritability, disinhibition, anxiety, sleeping, and eating. The frequency and severity of these symptoms are judged on a 4-point and 3-point scale, respectively. Scores range from 0-144 points, with a higher score indicating a worse outcome.
  measure: Cognition - Standardized Mini-Mental State Examination (sMMSE)
  time frame: Baseline (0 Weeks) to 22 Weeks
  description: Measures global cognition, and assesses orientation to time and place, immediate recall, short-term verbal memory, calculation, language, and construct ability. Scores range from 0-30 points, with a lower score indicating a worse outcome.
  measure: Weight
  time frame: Baseline (0 Weeks) to 22 Weeks
  description: Weight will be collected in kilograms. A change of 7% in weight will be considered clinically significant change.
  measure: Nutritional Status - Mini Nutritional Assessment - Short Form (MNA-SF)
  time frame: Baseline (0 Weeks) to 22 Weeks
  description: A structured interview consisting of 6 items that categorizes patients as malnourished, at risk of malnutrition, or of normal nutritional status. Scores range from 0-14 points, with a lower score indicating a worse outcome.
  measure: Pain - Pain Assessment Checklist for Seniors with Limited Ability to Communicate - II (PACSLAC-II)
  time frame: Baseline (0 Weeks) to 22 Weeks
  description: A 31-item observer-rated scale assessing facial expressions, activity/body movements, social/personality/mood indicators and mental status changes. Scores range form 0-31 points, with a higher score indicating a worse outcome.
  measure: Global Change - Alzheimer's Disease Cooperative Study - Clinical Global Impression of Severity/Change (ADCS-CGIS/C)
  time frame: Baseline (0 Weeks) to 22 Weeks
  description: A commonly-used clinician-rated scale that quantifies disease severity and clinical change (worsening, no change, or improvement), based on information regarding the patient's medical history, cognition, behaviour, and function. Scores range from 1-7, with a lower score indicating a worse outcome.
  measure: Sedation - Udvalg for Kliniske Undersøgelser (UKU) Side-Effect Rating Scale
  time frame: Baseline (0 Weeks) to 22 Weeks
  description: Sedation will be measured using the Sleepiness/Sedation subscale of the UKU-Side Effect Rating Scale. The UKU is a clinician-rated scale that assesses the side effects psychopharmacological medications. Scores range from 0-3, with a higher score indicating more sleepiness/sedation.
  arm group label: JZP541
  arm group type: Experimental
  description: Participants randomized to the JZP541 arm will be titrated up to a maximum dose of 26 mL/day
  arm group label: Placebo
  arm group type: Experimental
  description: Participants randomized to the placebo will be titrated up to a maximum dose of 26 mL/day
  intervention type: Drug
  intervention name: JZP541
  description: Participants in this arm will receive ZP541 for 8 weeks during the first treatment period. They will then receive a two-week single-blind placebo washout before moving into the second 8-week treatment period, during which they will receive the opposite study treatment than the one given in the first treatment period.
  arm group label: JZP541
  intervention type: Other
  intervention name: Placebo
  description: Participants in this arm will receive placebo for 8 weeks during the first treatment period. They will then receive a two-week single-blind placebo washout before moving into the second 8-week treatment period, during which they will receive the opposite study treatment than the one given in the first treatment period.
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 55 Years
  maximum age: N/A
  healthy volunteers: No
  facility: 
  facility: 
  facility: 
  country: Canada
  responsible party type: Sponsor
  mesh term: Alzheimer Disease
  sharing ipd: No