<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/NCT01682408</url>
  </required_header>
  <id_info>
    <org_study_id>D4300C00019</org_study_id>
    <nct_id>NCT01682408</nct_id>
  </id_info>
  <brief_title>Assess Pharmacokinetics of Fostamatinib in Fed and Fasted State in Combination With Ranitidine to Assess Bioavailability</brief_title>
  <acronym>PK Combination</acronym>
  <official_title>An Open-label, Single-center, 2-Part, Randomized Study to Assess the Pharmacokinetics of R406 in Healthy Subjects When Fostamatinib 150 mg is Administered Alone in Fed and Fasted State and in Combination With Ranitidine in Fasted State, and to Assess the Relative Bioavailability of Process Variants of Tablets</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <brief_summary>
    <textblock>
      Study to Assess the Pharmacokinetics of R406 in Healthy Subjects when Fostamatinib 150 mg is&#xD;
      Administered Alone in Fed and Fasted state and in Combination with Ranitidine in Fasted&#xD;
      State, and to Assess the Relative Bioavailability of Process Variants of Tablets&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An Open-label, Single-center, 2-Part, Randomized Study to Assess the Pharmacokinetics of R406&#xD;
      in Healthy Subjects when Fostamatinib 150 mg is Administered Alone in Fed and Fasted state&#xD;
      and in Combination with Ranitidine in Fasted State, and to Assess the Relative&#xD;
      Bioavailability of Process Variants of Tablets&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2012</completion_date>
  <primary_completion_date type="Actual">December 2012</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics profile of R406 in terms of maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC).</measure>
    <time_frame>Day 1 (predose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic profile of R406 in terms of area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-t)], time to Cmax (tmax), terminal half-life (t1/2λz), terminal rate constant (λz).</measure>
    <time_frame>Day 1 (predose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Description of the safety profile in terms of frequency of adverse events.</measure>
    <time_frame>up to 3 - 5 days after discharge</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Description of the safety profile in terms of severity of adverse events.</measure>
    <time_frame>up to 3 - 5 days after discharge</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Pharmacokinetics</condition>
  <arm_group>
    <arm_group_label>Part A1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference), fed 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference) 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed 150 mg ranitidine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 x 150mg mannitol based 38% drug-loaded tablet (batch variant A)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 x 150mg mannitol based 38% drug loaded tablet (batch variant B)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fostamatinib - 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference)</intervention_name>
    <description>1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference)</description>
    <arm_group_label>Part A1</arm_group_label>
    <arm_group_label>Part A2</arm_group_label>
    <arm_group_label>Part B3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fostamatinib - 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed</intervention_name>
    <description>3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed</description>
    <arm_group_label>Part A1</arm_group_label>
    <arm_group_label>Part A2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fostamatinib - 1 x 150mg mannitol based 38% drug-loaded tablet (batch variant A)</intervention_name>
    <description>1 x 150mg mannitol based 38% drug-loaded tablet (batch variant A)</description>
    <arm_group_label>Part B1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fostamatinib - 1 x 150mg mannitol based 38% drug loaded tablet (batch variant B)</intervention_name>
    <description>1 x 150mg mannitol based 38% drug loaded tablet(batch variant B)</description>
    <arm_group_label>Part B2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ranitidine</intervention_name>
    <description>150 mg ranitidine</description>
    <arm_group_label>Part A2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of signed and dated, written informed consent prior to any study-specific&#xD;
             procedures including the genetic sampling and analyses&#xD;
&#xD;
          -  Volunteers will be males or females aged 18 to 55 years (inclusive) and with a weight&#xD;
             of at least 50 kg and body mass index (BMI) between 18 and 30 kg/m2 inclusive.&#xD;
&#xD;
          -  Provision of signed, written, and dated informed consent for optional genetic&#xD;
             research. If a volunteer declines to participate in the genetic component of the&#xD;
             study, there will be no penalty or loss of benefit to the volunteer.&#xD;
&#xD;
          -  Male volunteers should be willing to use barrier contraception, ie, condoms from the&#xD;
             day of first dosing until 2 weeks after dosing with the IP in Treatment Period 5.&#xD;
&#xD;
          -  Females must have a negative pregnancy test at screening and on admission to the CPU&#xD;
             (including check-in at each treatment period), must not be lactating and must be of&#xD;
             non childbearing potential, confirmed at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of any clinically significant disease or disorder which, in the opinion of the&#xD;
             Investigator, may either put the volunteer at risk because of participation in the&#xD;
             study, or influence the results or the volunteer's ability to participate in the study&#xD;
&#xD;
          -  History or presence of GI, hepatic, or renal disease or any other condition known to&#xD;
             interfere with absorption, distribution, metabolism, or excretion of drugs&#xD;
&#xD;
          -  Any clinically significant illness, medical/surgical procedure, or trauma within 4&#xD;
             weeks of the first administration of IP&#xD;
&#xD;
          -  Any clinically significant abnormalities in clinical chemistry, hematology, or&#xD;
             urinalysis results as judged by the Investigator&#xD;
&#xD;
          -  Any positive result on screening for serum hepatitis B surface antigen, hepatitis C&#xD;
             antibody, and human immunodeficiency virus (HIV)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eleanor Lisbon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Quintiles Phase I unit 6700 w 115th st Overland Park, Ks 66211</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Christopher D O'Brien, MD PHD</last_name>
    <role>Study Director</role>
    <affiliation>AstraZeneca</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2012</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <last_update_submitted>December 27, 2012</last_update_submitted>
  <last_update_submitted_qc>December 27, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 28, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>R406,</keyword>
  <keyword>Fostamatinib,</keyword>
  <keyword>Phase I,</keyword>
  <keyword>Healthy Subjects,</keyword>
  <keyword>Pharmacokinetics,</keyword>
  <keyword>Fed/Fasted</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mannitol</mesh_term>
    <mesh_term>Ranitidine</mesh_term>
    <mesh_term>Ranitidine bismuth citrate</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/NCT01682408
org study id: D4300C00019
nct id: NCT01682408
lead sponsor: 
Study to Assess the Pharmacokinetics of R406 in Healthy Subjects when Fostamatinib 150 mg is
      Administered Alone in Fed and Fasted state and in Combination with Ranitidine in Fasted
      State, and to Assess the Relative Bioavailability of Process Variants of Tablets
An Open-label, Single-center, 2-Part, Randomized Study to Assess the Pharmacokinetics of R406
      in Healthy Subjects when Fostamatinib 150 mg is Administered Alone in Fed and Fasted state
      and in Combination with Ranitidine in Fasted State, and to Assess the Relative
      Bioavailability of Process Variants of Tablets
allocation: Randomized
primary purpose: Basic Science
masking: None (Open Label)
measure: Pharmacokinetics profile of R406 in terms of maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC).
time frame: Day 1 (predose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdose
measure: Pharmacokinetic profile of R406 in terms of area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-t)], time to Cmax (tmax), terminal half-life (t1/2λz), terminal rate constant (λz).
time frame: Day 1 (predose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdose
measure: Description of the safety profile in terms of frequency of adverse events.
time frame: up to 3 - 5 days after discharge
measure: Description of the safety profile in terms of severity of adverse events.
time frame: up to 3 - 5 days after discharge
arm group label: Part A1
arm group type: Active Comparator
description: 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference), fed 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed
arm group label: Part A2
arm group type: Active Comparator
description: 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference) 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed 150 mg ranitidine
arm group label: Part B1
arm group type: Active Comparator
description: 1 x 150mg mannitol based 38% drug-loaded tablet (batch variant A)
arm group label: Part B2
arm group type: Active Comparator
description: 1 x 150mg mannitol based 38% drug loaded tablet (batch variant B)
arm group label: Part B3
arm group type: Active Comparator
description: 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference)
intervention type: Drug
intervention name: Fostamatinib - 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference)
description: 1 x 150mg mannitol-based 38% drug-loaded tablet(orange reference)
arm group label: Part A1
arm group label: Part A2
arm group label: Part B3
intervention type: Drug
intervention name: Fostamatinib - 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed
description: 3 x 50mg microcrystalline cellulose-based 13% drug loaded tablets,(blue) fed
arm group label: Part A1
arm group label: Part A2
intervention type: Drug
intervention name: Fostamatinib - 1 x 150mg mannitol based 38% drug-loaded tablet (batch variant A)
description: 1 x 150mg mannitol based 38% drug-loaded tablet (batch variant A)
arm group label: Part B1
intervention type: Drug
intervention name: Fostamatinib - 1 x 150mg mannitol based 38% drug loaded tablet (batch variant B)
description: 1 x 150mg mannitol based 38% drug loaded tablet(batch variant B)
arm group label: Part B2
intervention type: Drug
intervention name: Ranitidine
description: 150 mg ranitidine
arm group label: Part A2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Eleanor Lisbon, MD
role: Principal Investigator
affiliation: Quintiles Phase I unit 6700 w 115th st Overland Park, Ks 66211
last name: Christopher D O'Brien, MD PHD
role: Study Director
affiliation: AstraZeneca
facility: 
country: United States
responsible party type: Sponsor
mesh term: Mannitol
mesh term: Ranitidine
mesh term: Ranitidine bismuth citrate