<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/NCT02215174</url>
  </required_header>
  <id_info>
    <org_study_id>14-13695.</org_study_id>
    <secondary_id>14-13695</secondary_id>
    <nct_id>NCT02215174</nct_id>
  </id_info>
  <brief_title>Rosuvastatin Interethnic PK Study</brief_title>
  <acronym>RST</acronym>
  <official_title>Rosuvastatin Pharmacokinetic (PK) Study in Caucasian and Asian Morbid Obese Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>E-DA Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Statins are the first-line and most commonly prescribed drugs for the prevention of&#xD;
      cardiovascular diseases and stroke in the world. Our preliminary studies suggest that&#xD;
      Caucasians might have a higher risk of developing potentially life-threatening drug-drug&#xD;
      interactions than Asians when taking statins. Drug-drug interactions occur in the body when&#xD;
      two or more drugs interact in a way that alters their effectiveness and/or toxicity. These&#xD;
      interactions are becoming an increasingly severe problem with statin usage since patients at&#xD;
      higher risk for cardiovascular diseases also take statins combined with many other drugs,&#xD;
      such as antihypertensive and diabetic drugs. Our study is aimed at understanding the&#xD;
      molecular factors and providing a sound basis for the interethnic dosage and response&#xD;
      differences for statins.&#xD;
&#xD;
      Drug-transporting proteins in intestine and liver tissues are responsible for taking up&#xD;
      statins into the blood. It is hypothesized that there are interethnic function differences of&#xD;
      these proteins and that they account for differences in statin blood levels between&#xD;
      Caucasians and Asians and the frequency and/or severity of their respective drug-drug&#xD;
      interactions. A clinical study will be conducted with Caucasian and Asian subjects undergoing&#xD;
      gastric bypass surgery so excess intestine and liver tissue can be acquired as part of the&#xD;
      standard procedure. Protein levels will be quantified in the tissues and correlate them with&#xD;
      different statin blood levels.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    IRB approval expired&#xD;
  </why_stopped>
  <start_date>February 2015</start_date>
  <completion_date type="Actual">December 6, 2018</completion_date>
  <primary_completion_date type="Actual">December 6, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area-under-the-concentration curve (AUC) of rosuvastatin</measure>
    <time_frame>0,1,2,3,4,5,6,8,12,24,36,48 hr post dosing</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in oral clearance of rosuvastatin</measure>
    <time_frame>Pre-surgery period: 48 hr after dosing; post-surgery period: 48 hr after dosing. Two periods separated by at least two months.</time_frame>
    <description>Changes in oral clearance of rosuvastatin within gastric bypass surgery will be analyzed using the ratio of areas under the systemic concentration curves (AUCs) from before to after surgery using the bioequivalence criteria of 80-125%. The oral clearance will be calculated based on the plasma data from each of the blood draws after the dosing period is completed (48hr). The pre and post surgery period are separated by at least a 8-week recovery period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Descriptive comparison of messenger ribonucleic acid (mRNA) and protein expression in the tissues</measure>
    <time_frame>Day of the surgery</time_frame>
    <description>Tissue samples will be collected on the day of the surgery.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Statin Pharmacokinetics Pre and Post Gastric Bypass Surgery</condition>
  <arm_group>
    <arm_group_label>Asians</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: Rosuvastatin Rosuvastatin 20mg po x1 Other Name: Crestor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Caucasians</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: Rosuvastatin Rosuvastatin 20mg po x1 Other Name: Crestor</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rosuvastatin</intervention_name>
    <description>Rosuvastatin 20mg po x1</description>
    <arm_group_label>Asians</arm_group_label>
    <arm_group_label>Caucasians</arm_group_label>
    <other_name>Crestor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects that are scheduled for bariatric surgery.&#xD;
&#xD;
          -  Subjects that are able and willing to donate surplus intestinal tissue.&#xD;
&#xD;
          -  Subjects with solute carrier organic anion transporter *1 (SLCO1B1) and breast cancer&#xD;
             resistant protein (BCRP) 421CC genotypes.&#xD;
&#xD;
          -  White/Caucasian/European and Asian/East Asian heritage individuals, male or female, 18&#xD;
             years of age or older.&#xD;
&#xD;
          -  BMI between 30-55 kg/m2&#xD;
&#xD;
          -  Be able to read, speak, and understand English(UCSF) and Chinese(Taiwan).&#xD;
&#xD;
          -  Subjects capable of providing informed consent and completing the requirements of the&#xD;
             study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with active liver and kidney problems, severe cardiovascular diseases, type I&#xD;
             diabetes, advanced pulmonary disease, and cancers.&#xD;
&#xD;
          -  Subjects on chronic prescription or over the counter medication that have previously&#xD;
             been reported to exhibit drug-drug interactions with rosuvastatin and cannot be&#xD;
             stopped two weeks prior to and during the study, including gemfibrozil, cyclosporine,&#xD;
             atazanavir, lopinavir and ritonavir.&#xD;
&#xD;
          -  Subjects incapable of multiple blood draws (HCT &lt; 30mg/dL).&#xD;
&#xD;
          -  Subjects with a history of rhabdomyolysis.&#xD;
&#xD;
          -  Subjects with a history of drug-related myalgias.&#xD;
&#xD;
          -  Subjects with a history or diagnosis of hemorrhagic tendencies or blood dyscrasias.&#xD;
&#xD;
          -  Subjects with a history of GI bleed or peptic ulcer disease.&#xD;
&#xD;
          -  Subjects with a recent history of trauma.&#xD;
&#xD;
          -  Subjects who smoke tobacco or have ongoing alcohol or illegal drug use.&#xD;
&#xD;
          -  Subjects who are pregnant, lactating, or trying to conceive during the study period.&#xD;
&#xD;
          -  Subjects allergic to rosuvastatin or any known component of the medications.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Leslie Benet, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>E-Da Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <zip>82445</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>January 15, 2020</last_update_submitted>
  <last_update_submitted_qc>January 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rosuvastatin</keyword>
  <keyword>PK</keyword>
  <keyword>Interethnic</keyword>
  <keyword>Morbid obese</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rosuvastatin Calcium</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/NCT02215174
org study id: 14-13695.
secondary id: 14-13695
nct id: NCT02215174
lead sponsor: 
collaborator: 
has dmc: No
Statins are the first-line and most commonly prescribed drugs for the prevention of
      cardiovascular diseases and stroke in the world. Our preliminary studies suggest that
      Caucasians might have a higher risk of developing potentially life-threatening drug-drug
      interactions than Asians when taking statins. Drug-drug interactions occur in the body when
      two or more drugs interact in a way that alters their effectiveness and/or toxicity. These
      interactions are becoming an increasingly severe problem with statin usage since patients at
      higher risk for cardiovascular diseases also take statins combined with many other drugs,
      such as antihypertensive and diabetic drugs. Our study is aimed at understanding the
      molecular factors and providing a sound basis for the interethnic dosage and response
      differences for statins.

      Drug-transporting proteins in intestine and liver tissues are responsible for taking up
      statins into the blood. It is hypothesized that there are interethnic function differences of
      these proteins and that they account for differences in statin blood levels between
      Caucasians and Asians and the frequency and/or severity of their respective drug-drug
      interactions. A clinical study will be conducted with Caucasian and Asian subjects undergoing
      gastric bypass surgery so excess intestine and liver tissue can be acquired as part of the
      standard procedure. Protein levels will be quantified in the tissues and correlate them with
      different statin blood levels.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Area-under-the-concentration curve (AUC) of rosuvastatin
time frame: 0,1,2,3,4,5,6,8,12,24,36,48 hr post dosing
measure: Change in oral clearance of rosuvastatin
time frame: Pre-surgery period: 48 hr after dosing; post-surgery period: 48 hr after dosing. Two periods separated by at least two months.
description: Changes in oral clearance of rosuvastatin within gastric bypass surgery will be analyzed using the ratio of areas under the systemic concentration curves (AUCs) from before to after surgery using the bioequivalence criteria of 80-125%. The oral clearance will be calculated based on the plasma data from each of the blood draws after the dosing period is completed (48hr). The pre and post surgery period are separated by at least a 8-week recovery period.
measure: Descriptive comparison of messenger ribonucleic acid (mRNA) and protein expression in the tissues
time frame: Day of the surgery
description: Tissue samples will be collected on the day of the surgery.
arm group label: Asians
arm group type: Experimental
description: Drug: Rosuvastatin Rosuvastatin 20mg po x1 Other Name: Crestor
arm group label: Caucasians
arm group type: Experimental
description: Drug: Rosuvastatin Rosuvastatin 20mg po x1 Other Name: Crestor
intervention type: Drug
intervention name: Rosuvastatin
description: Rosuvastatin 20mg po x1
arm group label: Asians
arm group label: Caucasians
other name: Crestor
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Leslie Benet, PhD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
facility: 
country: Taiwan
country: United States
responsible party type: Sponsor
mesh term: Rosuvastatin Calcium