<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/NCT03305471</url>
  </required_header>
  <id_info>
    <org_study_id>DS2330-A-U103</org_study_id>
    <nct_id>NCT03305471</nct_id>
  </id_info>
  <brief_title>DS2330b Alone and With Sevelamer in Patients on Chronic Hemodialysis</brief_title>
  <official_title>A Phase 1b Study, to Assess the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Repeated Doses of DS-2330b Alone and When Co-administered With Sevelamer in Patients on Chronic Hemodialysis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Daiichi Sankyo, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Daiichi Sankyo, 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>
      This three-part study will be performed with participants on chronic hemodialysis.&#xD;
&#xD;
        -  Part A will assess plasma pharmacokinetics of DS2330a (free form of DS2330b) after a&#xD;
           single dose of powder in bottle (PIB) or tablet formulations of DS2330b&#xD;
&#xD;
        -  Part B will test the safety, tolerability, and effects on serum phosphate (Pi) of 14-day&#xD;
           repeated oral doses of DS-2330b PIB when given alone and when given along with sevelamer&#xD;
           carbonate three times a day&#xD;
&#xD;
        -  Part C is optional, and will test the effects on serum phosphate (Pi) of 14-day repeated&#xD;
           oral doses of DS-2330b tablets when given with sevelamer carbonate&#xD;
&#xD;
      After screening, participants should expect the study to last about 21 days for Part A, and&#xD;
      46 days for Parts B and C.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 17, 2017</start_date>
  <completion_date type="Actual">January 3, 2019</completion_date>
  <primary_completion_date type="Actual">January 3, 2019</primary_completion_date>
  <phase>Phase 1</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 has a 2-period, open-label, randomized, 2-way crossover design with a single dose of Treatments A1 and A2&#xD;
Part B participants are randomized with a 2:3:3:3 ratio to Treatment B1, B2, B3, and B4, respectively, using a double-blind, repeated dose, parallel design&#xD;
Part C is an optional, single-arm, open label, repeated dose design</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Masking description is for Part B only - Parts A and C are Open Label, so have no masking</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Part A, Period 1: Maximum concentration (Cmax) of DS-2330a</measure>
    <time_frame>Period 1, Pre-dose to 48 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A, Period 2: Cmax of DS-2330a</measure>
    <time_frame>Period 2, Pre-dose to 48 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A, Period 1: Time to maximum concentration (Tmax) of DS-2330a</measure>
    <time_frame>Period 1, Pre-dose to 48 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A, Period 2: Tmax of DS-2330a</measure>
    <time_frame>Period 2, Pre-dose to 48 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A, Period 1: Area under the drug concentration curve (AUC) for DS-2330a over 24 hours (AUC-24)</measure>
    <time_frame>Period 1, Pre-dose to 24 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A, Period 2: AUC for DS-2330a for DS-2330a over 24 hours (AUC-24)</measure>
    <time_frame>Period 2, Pre-dose to 24 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A, Period 1: AUC at the last observable concentration (AUClast) and to infinity (AUCinf) for DS-2330a</measure>
    <time_frame>Period 1, Pre-dose to 48 hours post-dose</time_frame>
    <description>Categories (with the same unit of measure ng*hr/mL): AUClast, AUCinf</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A, Period 2: AUClast and AUCinf for DS-2330a</measure>
    <time_frame>Period 2, Pre-dose to 48 hours post-dose</time_frame>
    <description>Categories (with the same unit of measure ng*hr/mL): AUClast, AUCinf</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Parts B and C: Serum phosphate (Pi) levels before hemodialysis</measure>
    <time_frame>within 15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>All Parts: Number of trial participants with treatment-emergent adverse events (TEAEs)</measure>
    <time_frame>through trial completion (about 15 months)</time_frame>
    <description>TEAEs are adverse events (side effects) associated with taking an investigational product, whether or not they were caused by the investigational product. Clinically significant changes in physical exam findings, vital signs, electrocardiograms, clinical lab tests and thyroid function are recorded as TEAEs.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Parts B and C: Cmax of DS-2330a</measure>
    <time_frame>within 24 hours on Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parts B and C: Cmax of DS-2330a</measure>
    <time_frame>within 24 hours on Day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parts B and C: Tmax of DS-2330a</measure>
    <time_frame>within 24 hours, Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parts B and C: Tmax of DS-2330a</measure>
    <time_frame>within 24 hours, Day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parts B and C: AUC-24 for DS-2330a</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parts B and C: AUC-24 for DS-2330a</measure>
    <time_frame>Day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parts B and C: AUCinf for DS-2330a</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parts B and C: AUCinf for DS-2330a</measure>
    <time_frame>Day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parts B and C: Minimum concentration (Ctrough) of DS-2330a</measure>
    <time_frame>within 11 days</time_frame>
    <description>Trough blood levels for DS-2330a will be collected before the morning dose (prior to breakfast)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Dialysis clearance of DS-2330a</measure>
    <time_frame>on Day 11</time_frame>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Hyperphosphatemia</condition>
  <arm_group>
    <arm_group_label>Part A: DS-2330b PIB, then Tablet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>On a non-dialysis day, participants are given a single 250 mg dose of DS-2330b PIB [Treatment A1] right after breakfast. At least 3 days will be allowed to let the first dose wash out. Then on a non-dialysis day the participants are given a single 250 mg dose of DS-2330b in tablet form [Treatment A2] right after breakfast.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A: DS-2330b Tablet, then PIB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>On a non-dialysis day, participants are given a single 250 mg dose of DS-2330b in tablet form [Treatment A2] right after breakfast. At least 3 days will be allowed to let the first dose wash out. Then on a non-dialysis day the participants are given a single 250 mg dose of DS-2330b PIB [Treatment A1] right after breakfast.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants are given placebo three times daily [Treatment B1]</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: DS-2330b PIB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants are given 400 mg of DS-2330b PIB three times daily [Treatment B2]</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: DS-2330b PIB + Sevelamer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants are given 400 mg of DS-2330b PIB along with 1.6 grams of sevelamer three times daily [Treatment B3]</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Placebo + Sevelamer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants are given placebo along with 1.6 grams of sevelamer three times daily [Treatment B4]</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part C: DS-2330b Tablet + Sevelamer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants are given one 250 mg dose of DS-2330b in tablet form along with 1.6 grams of sevelamer three times daily [Treatment C]</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DS-2330b PIB</intervention_name>
    <description>DS-2330b as powder in bottle with stock solution (PIB)</description>
    <arm_group_label>Part A: DS-2330b PIB, then Tablet</arm_group_label>
    <arm_group_label>Part A: DS-2330b Tablet, then PIB</arm_group_label>
    <arm_group_label>Part B: DS-2330b PIB</arm_group_label>
    <arm_group_label>Part B: DS-2330b PIB + Sevelamer</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo matching stock solution in bottle</description>
    <arm_group_label>Part B: Placebo</arm_group_label>
    <arm_group_label>Part B: Placebo + Sevelamer</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sevelamer</intervention_name>
    <description>Sevelamer is a phosphate binder. It is used to decrease serum phosphate (Pi) level in people with chronic kidney disease who are on dialysis.</description>
    <arm_group_label>Part B: DS-2330b PIB + Sevelamer</arm_group_label>
    <arm_group_label>Part B: Placebo + Sevelamer</arm_group_label>
    <arm_group_label>Part C: DS-2330b Tablet + Sevelamer</arm_group_label>
    <other_name>Sevelamer carbonate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DS-2330b Tablet</intervention_name>
    <description>DS-2330b as tablet formulation</description>
    <arm_group_label>Part A: DS-2330b PIB, then Tablet</arm_group_label>
    <arm_group_label>Part A: DS-2330b Tablet, then PIB</arm_group_label>
    <arm_group_label>Part C: DS-2330b Tablet + Sevelamer</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has a body mass index (BMI) of 18 kg/m^2 to 40 kg/m^2 (inclusive)&#xD;
&#xD;
          -  Is on prescribed maintenance hemodialysis (three times a week) for at least 3 months&#xD;
             before Screening with adequacy demonstrated by a dialysis clearance within 3 months&#xD;
             before the first dose of the investigational medicinal product&#xD;
&#xD;
          -  Has permanent vascular access [arteriovenous (A-V) fistula or graft]&#xD;
&#xD;
          -  Is willing to comply with protocol-specified methods for family planning&#xD;
&#xD;
          -  For Parts B and C only:&#xD;
&#xD;
               1. Has protocol-specified acceptable serum Pi levels at Screening and in serum Pi&#xD;
                  after up to 3 weeks of washout from all Pi binders&#xD;
&#xD;
               2. Has protocol-specified acceptable serum Ca^2+ level and intact parathyroid&#xD;
                  hormone (iPTH) level at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is employed by the clinic or the sponsor&#xD;
&#xD;
          -  Has family relationship with another study participant&#xD;
&#xD;
          -  Has any history, current condition, or drug use that per protocol or in the opinion of&#xD;
             the investigator might compromise:&#xD;
&#xD;
               1. safety of the participant or their children&#xD;
&#xD;
               2. safety of study staff&#xD;
&#xD;
               3. analysis of study results&#xD;
&#xD;
          -  For Parts B and C only:&#xD;
&#xD;
               1. Is not able to take sevelamer carbonate&#xD;
&#xD;
               2. Has had partial or total parathyroidectomy within the last six months&#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>Global Clinical Leader</last_name>
    <role>Study Director</role>
    <affiliation>Daiichi Sankyo, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>DaVita Clinical Research</name>
      <address>
        <city>Lakewood</city>
        <state>Colorado</state>
        <zip>80228</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>DaVita Clinical Research</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prism Clinical Research</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>October 4, 2017</study_first_submitted>
  <study_first_submitted_qc>October 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 10, 2017</study_first_posted>
  <last_update_submitted>March 21, 2019</last_update_submitted>
  <last_update_submitted_qc>March 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chronic hemodialysis</keyword>
  <keyword>Investigational drug</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperphosphatemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sevelamer</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03305471
org study id: DS2330-A-U103
nct id: NCT03305471
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This three-part study will be performed with participants on chronic hemodialysis.

        -  Part A will assess plasma pharmacokinetics of DS2330a (free form of DS2330b) after a
           single dose of powder in bottle (PIB) or tablet formulations of DS2330b

        -  Part B will test the safety, tolerability, and effects on serum phosphate (Pi) of 14-day
           repeated oral doses of DS-2330b PIB when given alone and when given along with sevelamer
           carbonate three times a day

        -  Part C is optional, and will test the effects on serum phosphate (Pi) of 14-day repeated
           oral doses of DS-2330b tablets when given with sevelamer carbonate

      After screening, participants should expect the study to last about 21 days for Part A, and
      46 days for Parts B and C.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Part A has a 2-period, open-label, randomized, 2-way crossover design with a single dose of Treatments A1 and A2
Part B participants are randomized with a 2:3:3:3 ratio to Treatment B1, B2, B3, and B4, respectively, using a double-blind, repeated dose, parallel design
Part C is an optional, single-arm, open label, repeated dose design
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Masking description is for Part B only - Parts A and C are Open Label, so have no masking
measure: Part A, Period 1: Maximum concentration (Cmax) of DS-2330a
time frame: Period 1, Pre-dose to 48 hours post-dose
measure: Part A, Period 2: Cmax of DS-2330a
time frame: Period 2, Pre-dose to 48 hours post-dose
measure: Part A, Period 1: Time to maximum concentration (Tmax) of DS-2330a
time frame: Period 1, Pre-dose to 48 hours post-dose
measure: Part A, Period 2: Tmax of DS-2330a
time frame: Period 2, Pre-dose to 48 hours post-dose
measure: Part A, Period 1: Area under the drug concentration curve (AUC) for DS-2330a over 24 hours (AUC-24)
time frame: Period 1, Pre-dose to 24 hours post-dose
measure: Part A, Period 2: AUC for DS-2330a for DS-2330a over 24 hours (AUC-24)
time frame: Period 2, Pre-dose to 24 hours post-dose
measure: Part A, Period 1: AUC at the last observable concentration (AUClast) and to infinity (AUCinf) for DS-2330a
time frame: Period 1, Pre-dose to 48 hours post-dose
description: Categories (with the same unit of measure ng*hr/mL): AUClast, AUCinf
measure: Part A, Period 2: AUClast and AUCinf for DS-2330a
time frame: Period 2, Pre-dose to 48 hours post-dose
description: Categories (with the same unit of measure ng*hr/mL): AUClast, AUCinf
measure: Parts B and C: Serum phosphate (Pi) levels before hemodialysis
time frame: within 15 days
measure: All Parts: Number of trial participants with treatment-emergent adverse events (TEAEs)
time frame: through trial completion (about 15 months)
description: TEAEs are adverse events (side effects) associated with taking an investigational product, whether or not they were caused by the investigational product. Clinically significant changes in physical exam findings, vital signs, electrocardiograms, clinical lab tests and thyroid function are recorded as TEAEs.
measure: Parts B and C: Cmax of DS-2330a
time frame: within 24 hours on Day 1
measure: Parts B and C: Cmax of DS-2330a
time frame: within 24 hours on Day 13
measure: Parts B and C: Tmax of DS-2330a
time frame: within 24 hours, Day 1
measure: Parts B and C: Tmax of DS-2330a
time frame: within 24 hours, Day 13
measure: Parts B and C: AUC-24 for DS-2330a
time frame: Day 1
measure: Parts B and C: AUC-24 for DS-2330a
time frame: Day 13
measure: Parts B and C: AUCinf for DS-2330a
time frame: Day 1
measure: Parts B and C: AUCinf for DS-2330a
time frame: Day 13
measure: Parts B and C: Minimum concentration (Ctrough) of DS-2330a
time frame: within 11 days
description: Trough blood levels for DS-2330a will be collected before the morning dose (prior to breakfast)
measure: Part B: Dialysis clearance of DS-2330a
time frame: on Day 11
arm group label: Part A: DS-2330b PIB, then Tablet
arm group type: Experimental
description: On a non-dialysis day, participants are given a single 250 mg dose of DS-2330b PIB [Treatment A1] right after breakfast. At least 3 days will be allowed to let the first dose wash out. Then on a non-dialysis day the participants are given a single 250 mg dose of DS-2330b in tablet form [Treatment A2] right after breakfast.
arm group label: Part A: DS-2330b Tablet, then PIB
arm group type: Experimental
description: On a non-dialysis day, participants are given a single 250 mg dose of DS-2330b in tablet form [Treatment A2] right after breakfast. At least 3 days will be allowed to let the first dose wash out. Then on a non-dialysis day the participants are given a single 250 mg dose of DS-2330b PIB [Treatment A1] right after breakfast.
arm group label: Part B: Placebo
arm group type: Placebo Comparator
description: Participants are given placebo three times daily [Treatment B1]
arm group label: Part B: DS-2330b PIB
arm group type: Experimental
description: Participants are given 400 mg of DS-2330b PIB three times daily [Treatment B2]
arm group label: Part B: DS-2330b PIB + Sevelamer
arm group type: Experimental
description: Participants are given 400 mg of DS-2330b PIB along with 1.6 grams of sevelamer three times daily [Treatment B3]
arm group label: Part B: Placebo + Sevelamer
arm group type: Experimental
description: Participants are given placebo along with 1.6 grams of sevelamer three times daily [Treatment B4]
arm group label: Part C: DS-2330b Tablet + Sevelamer
arm group type: Experimental
description: Participants are given one 250 mg dose of DS-2330b in tablet form along with 1.6 grams of sevelamer three times daily [Treatment C]
intervention type: Drug
intervention name: DS-2330b PIB
description: DS-2330b as powder in bottle with stock solution (PIB)
arm group label: Part A: DS-2330b PIB, then Tablet
arm group label: Part A: DS-2330b Tablet, then PIB
arm group label: Part B: DS-2330b PIB
arm group label: Part B: DS-2330b PIB + Sevelamer
intervention type: Drug
intervention name: Placebo
description: Placebo matching stock solution in bottle
arm group label: Part B: Placebo
arm group label: Part B: Placebo + Sevelamer
intervention type: Drug
intervention name: Sevelamer
description: Sevelamer is a phosphate binder. It is used to decrease serum phosphate (Pi) level in people with chronic kidney disease who are on dialysis.
arm group label: Part B: DS-2330b PIB + Sevelamer
arm group label: Part B: Placebo + Sevelamer
arm group label: Part C: DS-2330b Tablet + Sevelamer
other name: Sevelamer carbonate
intervention type: Drug
intervention name: DS-2330b Tablet
description: DS-2330b as tablet formulation
arm group label: Part A: DS-2330b PIB, then Tablet
arm group label: Part A: DS-2330b Tablet, then PIB
arm group label: Part C: DS-2330b Tablet + Sevelamer
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Global Clinical Leader
role: Study Director
affiliation: Daiichi Sankyo, Inc.
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hyperphosphatemia
mesh term: Sevelamer