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/NCT05978063</url>
    </required_header>
    <id_info>
      <org_study_id>CR845-310601</org_study_id>
      <nct_id>NCT05978063</nct_id>
    </id_info>
    <brief_title>Study to Evaluate the Efficacy and Safety of Oral Difelikefalin for Moderate to Severe Pruritus in Subjects With Notalgia Paresthetica</brief_title>
    <official_title>A 2-part, Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Oral Difelikefalin for Moderate-to-Severe Pruritus in Adult Subjects With Notalgia Paresthetica</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Cara Therapeutics, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Cara Therapeutics, Inc.</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>
        This is a 2-part, multicenter, randomized, double-blind, placebo-controlled study to evaluate&#xD;
        the efficacy and safety of twice-daily (BID) oral difelikefalin for moderate-to-severe&#xD;
        pruritus in adult subjects with NP.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Part A of this study will evaluate the benefit-risk of 3 doses of difelikefalin compared to&#xD;
        placebo. The dose with the best benefit-risk profile will be further evaluated in Part B.&#xD;
        Part A of this study comprises a 28-day Screening Period, a 7-day Run-in Period, an 8-week&#xD;
        Double-blind Treatment Period, a 2-week Treatment Discontinuation Period, and a Safety&#xD;
        Follow-up Visit (14 days after the last dose of study treatment).&#xD;
  &#xD;
        Part B of this study will evaluate the efficacy, safety, and tolerability of oral&#xD;
        difelikefalin. The dose of oral difelikefalin to be assessed in Part B will depend on the&#xD;
        results of Part A. Part B of this study comprises a 28-day Screening Period, a 7-day Run-in&#xD;
        Period, an 8-week Double-blind Treatment Period, up to a 52-week OLE Period, and a Safety&#xD;
        Follow-up Visit.&#xD;
  &#xD;
        Subjects who participated in Part A of the study may not participate in Part B.&#xD;
  &#xD;
        All subjects will sign an informed consent form (ICF) and undergo screening for study&#xD;
        eligibility.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 1, 2023</start_date>
    <completion_date type="Anticipated">May 2026</completion_date>
    <primary_completion_date type="Anticipated">March 2026</primary_completion_date>
    <phase>Phase 2/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>Part A includes 4 arms and Part B includes 2 arms.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Proportion of subjects achieving ≥4-point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score</measure>
      <time_frame>Baseline, Week 8</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Proportion of subjects achieving ≥4-point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 4 in Part B</measure>
      <time_frame>Baseline, Week 4</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of subjects achieving ≥4-point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 2 in Part B</measure>
      <time_frame>Baseline, Week 2</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of subjects achieving ≥4-point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 1 in Part B</measure>
      <time_frame>Baseline, Week 1</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in the Numeric Rating Scale of Burning Sensation and Skin Tingling at Week 8 in Part B</measure>
      <time_frame>Baseline, Week 8</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of Subjects with H-IGA of Clear or Almost Clear at Week 8 in Part B</measure>
      <time_frame>Week 8</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of ≥4-point Improvement in Daily I-NRS at Day 2 in Part B</measure>
      <time_frame>Day 2</time_frame>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">440</enrollment>
    <condition>Pruritus</condition>
    <condition>Notalgia Paresthetica</condition>
    <arm_group>
      <arm_group_label>Difelikefalin 2.0 mg tablets</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Oral difelikefalin 2.0 mg tablet administered twice daily</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Difelikefalin 1.0 mg tablets</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Oral difelikefalin 1.0 mg tablet administered twice daily</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Difelikefalin 0.25 mg tablets</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Oral difelikefalin 0.25 mg tablet administered twice daily</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo tablets</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Oral placebo tablet administered twice daily</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>difelikefalin 2.0 mg tablets</intervention_name>
      <description>Oral difelikefalin 2.0 mg administered twice daily</description>
      <arm_group_label>Difelikefalin 2.0 mg tablets</arm_group_label>
      <other_name>CR845</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>difelikefalin 1.0 mg tablets</intervention_name>
      <description>Oral difelikefalin 1.0 mg administered twice daily</description>
      <arm_group_label>Difelikefalin 1.0 mg tablets</arm_group_label>
      <other_name>CR845</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>difelikefalin 0.25 mg tablets</intervention_name>
      <description>Oral difelikefalin 0.25 mg administered twice daily</description>
      <arm_group_label>Difelikefalin 0.25 mg tablets</arm_group_label>
      <other_name>CR845</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo tablets</intervention_name>
      <description>Oral Placebo administered twice daily</description>
      <arm_group_label>Placebo tablets</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Key Inclusion Criteria:&#xD;
  &#xD;
          To be eligible for inclusion into the study, a patient must meet the following criteria:&#xD;
  &#xD;
            -  Subject has clinically confirmed diagnosis of active Notalgia Paresthetica;&#xD;
  &#xD;
            -  Subject has a history of chronic pruritus due to Notalgia Paresthetica;&#xD;
  &#xD;
            -  Subject has moderate to severe pruritus;&#xD;
  &#xD;
            -  Female subject is not pregnant or nursing during any period of the study.&#xD;
  &#xD;
          Key Exclusion Criteria:&#xD;
  &#xD;
          A patient will be excluded from the study if any of the following criteria are met:&#xD;
  &#xD;
            -  Subject has pruritus attributed to a cause other than Notalgia Paresthetica;&#xD;
  &#xD;
            -  Subject has any clinically significant medical condition or&#xD;
               physical/laboratory/ECG/vital signs abnormality that would, in the opinion of the&#xD;
               investigator, put the subject at undue risk or interfere with interpretation of study&#xD;
               results.&#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>Cara Therapeutics</last_name>
      <role>Study Director</role>
      <affiliation>Cara Therapeutics</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Cara Therapeutics</last_name>
      <phone>203-406-3700</phone>
      <email>clinicaltrials.gov@caratherapeutics.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Cara Therapeutics Study Site</name>
        <address>
          <city>Hot Springs</city>
          <state>Arkansas</state>
          <zip>71913</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Cara Therapeutics Study Site</name>
        <address>
          <city>Los Angeles</city>
          <state>California</state>
          <zip>90045</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Cara Therapeutics Study Site</name>
        <address>
          <city>Coral Gables</city>
          <state>Florida</state>
          <zip>33134</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Cara Therapeutics Study Site</name>
        <address>
          <city>Metairie</city>
          <state>Louisiana</state>
          <zip>70006</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Cara Therapeutics Study Site</name>
        <address>
          <city>Houston</city>
          <state>Texas</state>
          <zip>77056</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Cara Therapeutics Study Site</name>
        <address>
          <city>Pflugerville</city>
          <state>Texas</state>
          <zip>78660</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 25, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>September 12, 2023</last_update_submitted>
    <last_update_submitted_qc>September 12, 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>
    <keyword>Notalgia Paresthetica</keyword>
    <keyword>Pruritus</keyword>
    <keyword>CR845</keyword>
    <keyword>Chronic Itch</keyword>
    <keyword>difelikefalin</keyword>
    <keyword>Itch</keyword>
    <keyword>Itching</keyword>
    <keyword>Generalized pruritus</keyword>
    <keyword>NP</keyword>
    <keyword>Neuropathic itch</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pruritus</mesh_term>
      <mesh_term>Back Pain</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/NCT05978063
  org study id: CR845-310601
  nct id: NCT05978063
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a 2-part, multicenter, randomized, double-blind, placebo-controlled study to evaluate
        the efficacy and safety of twice-daily (BID) oral difelikefalin for moderate-to-severe
        pruritus in adult subjects with NP.
  Part A of this study will evaluate the benefit-risk of 3 doses of difelikefalin compared to
        placebo. The dose with the best benefit-risk profile will be further evaluated in Part B.
        Part A of this study comprises a 28-day Screening Period, a 7-day Run-in Period, an 8-week
        Double-blind Treatment Period, a 2-week Treatment Discontinuation Period, and a Safety
        Follow-up Visit (14 days after the last dose of study treatment).
  
        Part B of this study will evaluate the efficacy, safety, and tolerability of oral
        difelikefalin. The dose of oral difelikefalin to be assessed in Part B will depend on the
        results of Part A. Part B of this study comprises a 28-day Screening Period, a 7-day Run-in
        Period, an 8-week Double-blind Treatment Period, up to a 52-week OLE Period, and a Safety
        Follow-up Visit.
  
        Subjects who participated in Part A of the study may not participate in Part B.
  
        All subjects will sign an informed consent form (ICF) and undergo screening for study
        eligibility.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Part A includes 4 arms and Part B includes 2 arms.
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: Proportion of subjects achieving ≥4-point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score
  time frame: Baseline, Week 8
  measure: Proportion of subjects achieving ≥4-point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 4 in Part B
  time frame: Baseline, Week 4
  measure: Proportion of subjects achieving ≥4-point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 2 in Part B
  time frame: Baseline, Week 2
  measure: Proportion of subjects achieving ≥4-point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 1 in Part B
  time frame: Baseline, Week 1
  measure: Change from Baseline in the Numeric Rating Scale of Burning Sensation and Skin Tingling at Week 8 in Part B
  time frame: Baseline, Week 8
  measure: Proportion of Subjects with H-IGA of Clear or Almost Clear at Week 8 in Part B
  time frame: Week 8
  measure: Proportion of ≥4-point Improvement in Daily I-NRS at Day 2 in Part B
  time frame: Day 2
  arm group label: Difelikefalin 2.0 mg tablets
  arm group type: Active Comparator
  description: Oral difelikefalin 2.0 mg tablet administered twice daily
  arm group label: Difelikefalin 1.0 mg tablets
  arm group type: Active Comparator
  description: Oral difelikefalin 1.0 mg tablet administered twice daily
  arm group label: Difelikefalin 0.25 mg tablets
  arm group type: Active Comparator
  description: Oral difelikefalin 0.25 mg tablet administered twice daily
  arm group label: Placebo tablets
  arm group type: Placebo Comparator
  description: Oral placebo tablet administered twice daily
  intervention type: Drug
  intervention name: difelikefalin 2.0 mg tablets
  description: Oral difelikefalin 2.0 mg administered twice daily
  arm group label: Difelikefalin 2.0 mg tablets
  other name: CR845
  intervention type: Drug
  intervention name: difelikefalin 1.0 mg tablets
  description: Oral difelikefalin 1.0 mg administered twice daily
  arm group label: Difelikefalin 1.0 mg tablets
  other name: CR845
  intervention type: Drug
  intervention name: difelikefalin 0.25 mg tablets
  description: Oral difelikefalin 0.25 mg administered twice daily
  arm group label: Difelikefalin 0.25 mg tablets
  other name: CR845
  intervention type: Drug
  intervention name: Placebo tablets
  description: Oral Placebo administered twice daily
  arm group label: Placebo tablets
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Cara Therapeutics
  role: Study Director
  affiliation: Cara Therapeutics
  last name: Cara Therapeutics
  phone: 203-406-3700
  email: clinicaltrials.gov@caratherapeutics.com
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  country: United States
  responsible party type: Sponsor
  mesh term: Pruritus
  mesh term: Back Pain
  sharing ipd: No