<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/NCT02229929</url>
  </required_header>
  <id_info>
    <org_study_id>CR845-CLIN2005</org_study_id>
    <nct_id>NCT02229929</nct_id>
  </id_info>
  <brief_title>Safety and Pharmacokinetics of IV CR845 in Hemodialysis Patients, and Its Efficacy in Patients With Uremic Pruritus</brief_title>
  <official_title>A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Pharmacokinetics of Intravenous CR845 in Hemodialysis Patients, and Its Safety and Efficacy in Hemodialysis Patients With Uremic Pruritus</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>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary purpose of this study is to:&#xD;
&#xD;
        -  Evaluate the safety and pharmacokinetic profile of repeated doses IV CR845 over one week&#xD;
           in patients who are undergoing hemodialysis. (Part A)&#xD;
&#xD;
        -  This study is also investigating whether repeated doses of IV CR845 over two weeks is&#xD;
           safe and effective in reducing the intensity of itching in hemodialysis patients with&#xD;
           uremic pruritus (Part B).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Placebo-controlled&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part A: Determine the Pharmacokinetics of Repeated Doses of CR845 in Hemodialysis Patients (half-life, Cmax, Tmax, AUC, Vd)</measure>
    <time_frame>1 week</time_frame>
    <description>To evaluate the pharmacokinetics of repeated doses of CR845 in hemodialysis patients over a one-week treatment period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Change in Worst Itching Intensity using a 100-mm Visual Analog Scale</measure>
    <time_frame>2 weeks</time_frame>
    <description>Change from baseline to the average of Week 2 worst itching (daytime and nighttime) VAS where 0 mm represents &quot;No Itch&quot; and 100 mm represents the &quot;Worst Itch You Can Imagine&quot;.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part B: Change in quality-of-life assessed using the Skindex-10 survey</measure>
    <time_frame>2 weeks</time_frame>
    <description>Change from baseline to Day 15 in itch-related quality of life as assessed by the total Skindex-10 scores</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Sleep disturbance assessed using Itch Medical Outcomes Study (MOS) survey</measure>
    <time_frame>2 weeks</time_frame>
    <description>Change from baseline to Day 15 in itch-related sleep disturbance based on the Itch MOS sleep problems index II (SLP-9)</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">89</enrollment>
  <condition>Pruritus</condition>
  <condition>Uremic Pruritus</condition>
  <arm_group>
    <arm_group_label>Part A: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intravenous matched placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A: CR845 0.5 mcg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous CR845, 0.5 mcg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A: CR845 1.0 mcg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous CR845, 1.0 mcg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A: CR845 2.5 mcg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous CR845, 2.5 mcg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intravenous matched placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: CR845 1.0 mcg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous CR845, 1.0 mcg/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Part A: Placebo</intervention_name>
    <description>Part A: Single i.v. dose of Placebo administered after each dialysis session over a 1 week treatment period (3 times per week)</description>
    <arm_group_label>Part A: Placebo</arm_group_label>
    <other_name>Matched Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Part A: CR845 0.5 mcg/kg</intervention_name>
    <description>Part A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week)</description>
    <arm_group_label>Part A: CR845 0.5 mcg/kg</arm_group_label>
    <other_name>CR845 0.5 mcg/kg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Part A: CR845 1.0 mcg/kg</intervention_name>
    <description>Part A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week)</description>
    <arm_group_label>Part A: CR845 1.0 mcg/kg</arm_group_label>
    <other_name>CR845 1.0 mcg/kg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Part A: CR845 2.5 mcg/kg</intervention_name>
    <description>Part A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week)</description>
    <arm_group_label>Part A: CR845 2.5 mcg/kg</arm_group_label>
    <other_name>CR845 2.5 mcg/kg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Part B: Placebo</intervention_name>
    <description>Part B: Single i.v. dose of Placebo administered after each dialysis session over a 2 week treatment period (3 times per week)</description>
    <arm_group_label>Part B: Placebo</arm_group_label>
    <other_name>Matched Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Part B: CR845 1.0 mcg/kg</intervention_name>
    <description>Part B: Single i.v. dose of CR845 administered after each dialysis session over a 2 week treatment period (3 times per week)</description>
    <arm_group_label>Part B: CR845 1.0 mcg/kg</arm_group_label>
    <other_name>CR845 1.0 mcg/kg</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Able to provide written informed consent prior to any study procedures;&#xD;
&#xD;
          -  Able to communicate clearly with the Investigator and staff, able to read and&#xD;
             understand the study procedures;&#xD;
&#xD;
          -  Males or females 18 years of age or older;&#xD;
&#xD;
          -  End stage renal disease (ESRD) patients who have been on hemodialysis for at least&#xD;
             three months and are currently on hemodialysis:&#xD;
&#xD;
               -  At least three times per week (Part A)&#xD;
&#xD;
               -  Three times per week (Part B)&#xD;
&#xD;
          -  Has a body weight ≤ 135 kg&#xD;
&#xD;
          -  Part B: Patient who self-reports daily or near daily pruritus during the 6 weeks prior&#xD;
             to Screening;&#xD;
&#xD;
          -  Part B: Patient who reports a Patient B or Patient C profile on the Patient&#xD;
             Self-categorization of Pruritus Disease Severity questionnaire at Screening;&#xD;
&#xD;
          -  Part B: At the end of the Run-in Period:&#xD;
&#xD;
               -  Patient who completed ratings of worst itching intensity [visual analog scale&#xD;
                  (VAS)] at least 8 times out of 14 VAS assessments;&#xD;
&#xD;
               -  Patient who has a mean value of &gt;40 mm on the worst itching VAS over the one week&#xD;
                  Run-in Period.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Known to be non-compliant with dialysis treatment (i.e., has a history of missed&#xD;
             dialysis sessions due to non-compliance in the past 2 months);&#xD;
&#xD;
          -  Anticipated to receive a kidney transplant during the study;&#xD;
&#xD;
          -  Known history of allergic reaction to opiates such as hives (Note: side effects&#xD;
             related to the use of opioids such as constipation or nausea would not exclude the&#xD;
             patients from the study);&#xD;
&#xD;
          -  Known or suspected history of Diagnostic and Statistical Manual of Mental Disorders,&#xD;
             Fifth Edition (DSM-5)-diagnosed alcohol, narcotic, or other drug abuse or dependence&#xD;
             within 12 months prior to Screening;&#xD;
&#xD;
          -  Acute or unstable medical condition(s) such as congestive heart failure [New York&#xD;
             Heart Association (NYHA) class IV], which in the opinion of the Investigator would&#xD;
             pose undue risk to the patient or would impede complete collection of the data or its&#xD;
             evaluability;&#xD;
&#xD;
          -  Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) greater than&#xD;
             2.5X the reference upper limit of normal (ULN), or bilirubin greater than 4X the ULN&#xD;
             at Screening;&#xD;
&#xD;
          -  Received another investigational drug within 30 days prior to the start of the Run-in&#xD;
             Period or has planned to participate in another clinical trial while enrolled in this&#xD;
             study&#xD;
&#xD;
          -  Part B: Has pruritus probably or definitely attributed to a cause other than ESRD or&#xD;
             its complications (e.g., patients with concomitant pruritic dermatological disease or&#xD;
             cholestatic liver disease would be excluded). (Note: Patients whose pruritus is&#xD;
             attributed to ESRD complications such as hyperparathyroidism, hyperphosphatemia,&#xD;
             anemia, or the dialysis procedure or prescription may be enrolled);&#xD;
&#xD;
          -  Part B: Has localized itch restricted to the palms of the hands as determined from the&#xD;
             Brief Itch Inventory diagram, completed during the Screening Period;&#xD;
&#xD;
          -  Part B: Has pruritus only during the dialysis session (by patient report);&#xD;
&#xD;
          -  Part B: Has used gabapentin, calcineurin inhibitors, opioids; antipsychotics; systemic&#xD;
             or topical corticosteroids (other than otic or ophthalmic preparations); sedatives;&#xD;
             hypnotics; anti-anxiety agents selective serotonin reuptake inhibitors (SSRIs); or&#xD;
             tricyclic antidepressants for &lt; 4 weeks prior to the start of the Run-In Period or had&#xD;
             a dose change within the previous 30 days;&#xD;
&#xD;
          -  Part B: Is not willing to abstain from use of antihistamines (oral, IV, or topical)&#xD;
             for 3 weeks (from the start of the Run-In Period through the end of Week 2);&#xD;
&#xD;
          -  Part B: Not willing to abstain from making changes to topical non-drug treatments&#xD;
             (e.g., emollients, creams, oils) for pruritus for 3 weeks (from the start of the&#xD;
             Run-In Period through the end of Week 2);&#xD;
&#xD;
          -  Part B: Received ultraviolet B treatment within 30 days prior to the start of the&#xD;
             Run-in Period.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frederique Menzaghi, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Cara Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>US Renal Care</name>
      <address>
        <city>Pine Bluff</city>
        <state>Arkansas</state>
        <zip>71603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US Renal Care</name>
      <address>
        <city>Chula Vista</city>
        <state>California</state>
        <zip>91915</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US Renal Care</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Valley Renal Medical Group</name>
      <address>
        <city>Northridge</city>
        <state>California</state>
        <zip>91324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nephrology Specialists Medical Group, Inc</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North American Research Institute</name>
      <address>
        <city>San Dimas</city>
        <state>California</state>
        <zip>91773</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida College of Medicine Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orlando Clinical Research Center</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32809</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pines Clinical Research, Inc.</name>
      <address>
        <city>Pembroke Pines</city>
        <state>Florida</state>
        <zip>33028</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory Dialysis Center at Northside</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30318</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western New England Renal &amp; Transplant Associates, PC</name>
      <address>
        <city>Springfield</city>
        <state>Massachusetts</state>
        <zip>01107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US Renal Care</name>
      <address>
        <city>Gallup</city>
        <state>New Mexico</state>
        <zip>87301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trude Weishaupt Memorial Dialysis Center</name>
      <address>
        <city>Fresh Meadows</city>
        <state>New York</state>
        <zip>11365</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winthrop University Hospital</name>
      <address>
        <city>Mineola</city>
        <state>New York</state>
        <zip>11501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brookview Hills Research Associates, LLC</name>
      <address>
        <city>Winston Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US Renal Care</name>
      <address>
        <city>Aiken</city>
        <state>South Carolina</state>
        <zip>29803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeast Renal Research Institute</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37408</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US Renal Care</name>
      <address>
        <city>Grand Prairie</city>
        <state>Texas</state>
        <zip>75050</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US Renal Care</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>August 27, 2014</study_first_submitted>
  <study_first_submitted_qc>August 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <disposition_first_submitted>August 8, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>August 8, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">August 10, 2016</disposition_first_posted>
  <last_update_submitted>August 8, 2016</last_update_submitted>
  <last_update_submitted_qc>August 8, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 10, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pruritus</keyword>
  <keyword>uremic pruritus</keyword>
  <keyword>kappa opioid</keyword>
  <keyword>CR845</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pruritus</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT02229929
org study id: CR845-CLIN2005
nct id: NCT02229929
lead sponsor: 
has dmc: No
The primary purpose of this study is to:

        -  Evaluate the safety and pharmacokinetic profile of repeated doses IV CR845 over one week
           in patients who are undergoing hemodialysis. (Part A)

        -  This study is also investigating whether repeated doses of IV CR845 over two weeks is
           safe and effective in reducing the intensity of itching in hemodialysis patients with
           uremic pruritus (Part B).
Placebo-controlled
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Part A: Determine the Pharmacokinetics of Repeated Doses of CR845 in Hemodialysis Patients (half-life, Cmax, Tmax, AUC, Vd)
time frame: 1 week
description: To evaluate the pharmacokinetics of repeated doses of CR845 in hemodialysis patients over a one-week treatment period.
measure: Part B: Change in Worst Itching Intensity using a 100-mm Visual Analog Scale
time frame: 2 weeks
description: Change from baseline to the average of Week 2 worst itching (daytime and nighttime) VAS where 0 mm represents "No Itch" and 100 mm represents the "Worst Itch You Can Imagine".
measure: Part B: Change in quality-of-life assessed using the Skindex-10 survey
time frame: 2 weeks
description: Change from baseline to Day 15 in itch-related quality of life as assessed by the total Skindex-10 scores
measure: Part B: Sleep disturbance assessed using Itch Medical Outcomes Study (MOS) survey
time frame: 2 weeks
description: Change from baseline to Day 15 in itch-related sleep disturbance based on the Itch MOS sleep problems index II (SLP-9)
arm group label: Part A: Placebo
arm group type: Placebo Comparator
description: Intravenous matched placebo
arm group label: Part A: CR845 0.5 mcg/kg
arm group type: Experimental
description: Intravenous CR845, 0.5 mcg/kg
arm group label: Part A: CR845 1.0 mcg/kg
arm group type: Experimental
description: Intravenous CR845, 1.0 mcg/kg
arm group label: Part A: CR845 2.5 mcg/kg
arm group type: Experimental
description: Intravenous CR845, 2.5 mcg/kg
arm group label: Part B: Placebo
arm group type: Placebo Comparator
description: Intravenous matched placebo
arm group label: Part B: CR845 1.0 mcg/kg
arm group type: Experimental
description: Intravenous CR845, 1.0 mcg/kg
intervention type: Drug
intervention name: Part A: Placebo
description: Part A: Single i.v. dose of Placebo administered after each dialysis session over a 1 week treatment period (3 times per week)
arm group label: Part A: Placebo
other name: Matched Placebo
intervention type: Drug
intervention name: Part A: CR845 0.5 mcg/kg
description: Part A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week)
arm group label: Part A: CR845 0.5 mcg/kg
other name: CR845 0.5 mcg/kg
intervention type: Drug
intervention name: Part A: CR845 1.0 mcg/kg
description: Part A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week)
arm group label: Part A: CR845 1.0 mcg/kg
other name: CR845 1.0 mcg/kg
intervention type: Drug
intervention name: Part A: CR845 2.5 mcg/kg
description: Part A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week)
arm group label: Part A: CR845 2.5 mcg/kg
other name: CR845 2.5 mcg/kg
intervention type: Drug
intervention name: Part B: Placebo
description: Part B: Single i.v. dose of Placebo administered after each dialysis session over a 2 week treatment period (3 times per week)
arm group label: Part B: Placebo
other name: Matched Placebo
intervention type: Drug
intervention name: Part B: CR845 1.0 mcg/kg
description: Part B: Single i.v. dose of CR845 administered after each dialysis session over a 2 week treatment period (3 times per week)
arm group label: Part B: CR845 1.0 mcg/kg
other name: CR845 1.0 mcg/kg
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Frederique Menzaghi, PhD
role: Study Director
affiliation: Cara Therapeutics, Inc.
facility: 
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country: United States
responsible party type: Sponsor
mesh term: Pruritus