<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/NCT01675973</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-259-0112</org_study_id>
    <nct_id>NCT01675973</nct_id>
  </id_info>
  <brief_title>A Phase 1 Study to Assess the Effect of Severe Renal Impairment on the Pharmacokinetics, as Well as Safety/Tolerability, of Ranolazine</brief_title>
  <official_title>A Phase 1, Parallel-group, Open-label, Multiple-dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Ranolazine ER in Subjects With Severe Renal Impairment as Compared to Healthy Subjects With Normal Renal Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gilead Sciences</source>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the effect of severe renal impairment on the&#xD;
      steady-state PK, as well as safety and tolerability, of ranolazine, compared to subjects with&#xD;
      normal renal function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to assess the effects of severe renal impairment (RI)&#xD;
      on the steady-state pharmacokinetics (PK) of ranolazine and key metabolites. The secondary&#xD;
      objective of this study is to assess the safety and tolerability of multiple oral doses of&#xD;
      ranolazine in subjects with severe RI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study met stopping criteria specified within protocol.&#xD;
  </why_stopped>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">August 2012</completion_date>
  <primary_completion_date type="Actual">August 2012</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the plasma concentration vs time curve over the dosing interval at steady state (AUCtau) and Maximum observed plasma concentration at steady-state (Cmax)</measure>
    <time_frame>Day 7 for Cohorts A &amp; B, and Day -1 for Cohort B only.</time_frame>
    <description>Maximum observed plasma ranolazine concentration at steady-state (Cmax) [Time frame: 0, 1, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 7 for Cohort A and Days -1 and 7 for Cohort B]&#xD;
Area under the plasma ranolazine concentration versus time curve over the dosing interval at steady state (AUCtau) [Time frame: 0, 1, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 7 for Cohort A and Days -1 and 7 for Cohort B]</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with AEs</measure>
    <time_frame>From Day -5 for Cohort B or Day 1 for Cohort A through the 14-day follow-up.</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Severe Renal Impairment</condition>
  <arm_group>
    <arm_group_label>Subjects with severe renal impairment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort B (subjects with severe RI): Approximately 10 subjects will be enrolled to obtain approximately 8 evaluable subjects.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Subjects with normal renal function</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort A (healthy subjects with normal renal function): Approximately 10 subjects will be enrolled to obtain approximately 8 evaluable subjects.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RANEXA</intervention_name>
    <description>500mg BID up to 1000mg BID</description>
    <arm_group_label>Subjects with normal renal function</arm_group_label>
    <arm_group_label>Subjects with severe renal impairment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria (All Cohorts):&#xD;
&#xD;
          -  Males and females, 18 to 75 years old, inclusive&#xD;
&#xD;
          -  Body mass index (BMI) 18 to 40 kg/m2, inclusive, at Screening&#xD;
&#xD;
          -  Females of child-bearing potential must have a negative pregnancy test at Screening&#xD;
             and on Day -1 (Cohort A) or Day -6 (Cohort B) and must agree to use highly effective&#xD;
             contraception methods from Screening throughout the duration of the Treatment Period&#xD;
             and for 14 days following the last dose of study drug&#xD;
&#xD;
        Inclusion criteria (Cohort A [Healthy subjects with normal renal function] only):&#xD;
&#xD;
          -  Estimated creatinine clearance (CLCR), according to the Cockcroft-Gault (C-G)&#xD;
             equation, ≥ 90 mL/min at Screening&#xD;
&#xD;
          -  Age, BMI, and sex comparable to those of subjects of Cohort B&#xD;
&#xD;
          -  Good health status as determined by no clinically significant deviation from normal in&#xD;
             medical history, physical examination, ECGs, and clinical laboratory determinations&#xD;
&#xD;
        Inclusion criteria (Cohort B, Severe RI):&#xD;
&#xD;
          -  Diagnosis of CKD&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR), according to the Modification of Diet in&#xD;
             Renal Disease (MDRD) equation, &lt; 30 mL/min/1.73 m2 (and not receiving dialysis)&#xD;
&#xD;
          -  Stable medication dose and dosing regimen for treatment of the complications of renal&#xD;
             disease or other concomitant chronic illnesses for at least 2 weeks prior to study&#xD;
             drug administration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Exclusion criteria (All Cohorts):&#xD;
&#xD;
          -  History of uncontrolled or unstable cardiovascular, respiratory, hepatic,&#xD;
             gastrointestinal, endocrine, hematopoietic, psychiatric, and/or neurological disease&#xD;
&#xD;
          -  Current or recent (within 3 months) gastrointestinal (GI) disease or any GI surgery&#xD;
             that could impact absorption of study drug&#xD;
&#xD;
          -  Any major surgery within 4 weeks of dosing with study drug&#xD;
&#xD;
          -  Donation of blood or plasma to a blood bank or in a clinical study (except a screening&#xD;
             visit) within 4 weeks of dosing with study drug&#xD;
&#xD;
          -  Blood transfusion within 4 weeks of dosing with study drug&#xD;
&#xD;
          -  Consumption of &gt; 14 alcoholic drinks per week, or more than 4 alcoholic drinks on any&#xD;
             one day&#xD;
&#xD;
          -  History of regular use of tobacco- or nicotine-containing products in excess of 10&#xD;
             cigarettes per day or equivalent&#xD;
&#xD;
          -  History of substance abuse within 12 months prior to Screening&#xD;
&#xD;
          -  Positive drug screen&#xD;
&#xD;
          -  Positive alcohol test&#xD;
&#xD;
          -  Clinically significant history of hepatic disease&#xD;
&#xD;
          -  QTcF interval &gt; 480 msec at Screening or Day -6 (for Cohort B) or Day -1 (for Cohort&#xD;
             A)&#xD;
&#xD;
          -  History of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia, or&#xD;
             torsade de pointes&#xD;
&#xD;
          -  Known hypersensitivity or previous intolerance to ranolazine or any of its excipients&#xD;
&#xD;
          -  Treatment with selected medications&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Other condition(s) that, in the opinion of the Investigator, would prevent compliance&#xD;
             with the study protocol&#xD;
&#xD;
        Exclusion criteria (Cohort A [Healthy subjects with normal renal function] only):&#xD;
&#xD;
          -  Evidence of organ dysfunction or any clinically significant deviation from normal in&#xD;
             physical examination, vital signs, ECG, or clinical laboratory determinations&#xD;
&#xD;
          -  Hemoglobin &lt; 12 g/dL for males, &lt; 11 g/dL for females at Screening&#xD;
&#xD;
          -  Any prescription and over-the-counter medications, including herbal products&#xD;
&#xD;
        Exclusion criteria (Cohort B, Severe RI):&#xD;
&#xD;
          -  Any clinical, ECG, and laboratory findings beyond those which are consistent with the&#xD;
             degree of renal dysfunction&#xD;
&#xD;
          -  History of or anticipated near-term need for renal transplant (within 3 months)&#xD;
&#xD;
          -  History of hemodialysis or peritoneal dialysis within 1 year prior to Screening, or&#xD;
             anticipated need for hemodialysis or peritoneal dialysis during the study&#xD;
&#xD;
          -  History of acute renal failure or nephrotic syndrome within 1 year prior to Screening&#xD;
&#xD;
          -  History of diabetic ketoacidosis&#xD;
&#xD;
          -  History of severe hypoglycemia&#xD;
&#xD;
          -  Other condition(s) that, in the opinion of the Investigator, would prevent compliance&#xD;
             with the study protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Clinical Pharmacology of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2012</verification_date>
  <study_first_submitted>July 26, 2012</study_first_submitted>
  <study_first_submitted_qc>August 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 30, 2012</study_first_posted>
  <last_update_submitted>December 4, 2012</last_update_submitted>
  <last_update_submitted_qc>December 4, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 6, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ranolazine</keyword>
  <keyword>renal impairment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Renal Insufficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ranolazine</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/NCT01675973
org study id: GS-US-259-0112
nct id: NCT01675973
lead sponsor: 
The purpose of this study is to assess the effect of severe renal impairment on the
      steady-state PK, as well as safety and tolerability, of ranolazine, compared to subjects with
      normal renal function.
The primary objective of this study is to assess the effects of severe renal impairment (RI)
      on the steady-state pharmacokinetics (PK) of ranolazine and key metabolites. The secondary
      objective of this study is to assess the safety and tolerability of multiple oral doses of
      ranolazine in subjects with severe RI.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the plasma concentration vs time curve over the dosing interval at steady state (AUCtau) and Maximum observed plasma concentration at steady-state (Cmax)
time frame: Day 7 for Cohorts A & B, and Day -1 for Cohort B only.
description: Maximum observed plasma ranolazine concentration at steady-state (Cmax) [Time frame: 0, 1, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 7 for Cohort A and Days -1 and 7 for Cohort B]
Area under the plasma ranolazine concentration versus time curve over the dosing interval at steady state (AUCtau) [Time frame: 0, 1, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 7 for Cohort A and Days -1 and 7 for Cohort B]
measure: Number of subjects with AEs
time frame: From Day -5 for Cohort B or Day 1 for Cohort A through the 14-day follow-up.
arm group label: Subjects with severe renal impairment
arm group type: Experimental
description: Cohort B (subjects with severe RI): Approximately 10 subjects will be enrolled to obtain approximately 8 evaluable subjects.
arm group label: Subjects with normal renal function
arm group type: Experimental
description: Cohort A (healthy subjects with normal renal function): Approximately 10 subjects will be enrolled to obtain approximately 8 evaluable subjects.
intervention type: Drug
intervention name: RANEXA
description: 500mg BID up to 1000mg BID
arm group label: Subjects with normal renal function
arm group label: Subjects with severe renal impairment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Renal Insufficiency
mesh term: Ranolazine