<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/NCT01714154</url>
  </required_header>
  <id_info>
    <org_study_id>NP28326</org_study_id>
    <secondary_id>2012-002283-28</secondary_id>
    <nct_id>NCT01714154</nct_id>
  </id_info>
  <brief_title>A Safety And Pharmacokinetic Study of Setrobuvir Alone and In Combination With Ritonavir-Boosted Danoprevir in Subjects With Mild Hepatic Impairment Compared to Healthy Controls</brief_title>
  <official_title>A Multi Center, Sequential, Open-Label, Multiple-Dose Study of Setrobuvir (STV) Alone and With Co-Administration of Ritonavir-boosted Danoprevir to Evaluate the Safety, Tolerability and Pharmacokinetics of STV, DNV, and Ritonavir (RTV) in Subjects With Mild Hepatic Impairment Compared to Healthy Controls</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <brief_summary>
    <textblock>
      This multi-center, fixed-sequence, open-label, multiple-dose, 2-period study will evaluate&#xD;
      the safety, tolerability and pharmacokinetics of setrobuvir alone or in combination with&#xD;
      ritonavir-boosted danoprevir in subjects with mild hepatic impairment compared to healthy&#xD;
      controls. All subjects will receive multiple doses of setrobuvir orally for 10 days in Period&#xD;
      1 and multiple doses of setrobuvir plus ritonavir-boosted danoprevir orally for 10 days in&#xD;
      Period 2, with a washout phase of at least 9 days between treatments.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">May 2013</completion_date>
  <primary_completion_date type="Actual">May 2013</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>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety: Incidence of adverse events</measure>
    <time_frame>approximately 40 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Maximum plasma concentration at steady-state (Css,max)</measure>
    <time_frame>up to 16 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Total area under the concentration-time curve form time 0 to 12 hours post-dose at steady-state (AUCss,0-12h)</measure>
    <time_frame>up to 16 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Plasma concentration at steady-state 12 hours post-dose (Css, 12h)</measure>
    <time_frame>up to 16 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Time to maximum plasma concentration (tmax)</measure>
    <time_frame>up to 16 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Elimination half-life (t1/2)</measure>
    <time_frame>up to 16 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Apparent oral clearance at steady-state (CLss/F)</measure>
    <time_frame>up to 16 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Cumulative amount excreted at steady-state (Aess)</measure>
    <time_frame>up to 16 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Fraction of orally administered drug excreted into urine (fe/f)</measure>
    <time_frame>up to 16 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of danoprevir in combination with setrobuvir: Area under the concentration-time curve (AUC)</measure>
    <time_frame>up to 12 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of ritonavir in combination with setrobuvir: Area under the concentration-time curve (AUC)</measure>
    <time_frame>up to 12 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Healthy Volunteer</condition>
  <arm_group>
    <arm_group_label>A: setrobuvir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>B: setrobuvir + DNV/r</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>danoprevir</intervention_name>
    <description>100 mg orally every 12 hours</description>
    <arm_group_label>B: setrobuvir + DNV/r</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ritonavir</intervention_name>
    <description>100 mg orally every 12 hours</description>
    <arm_group_label>B: setrobuvir + DNV/r</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>setrobuvir</intervention_name>
    <description>200 mg orally every 12 hours</description>
    <arm_group_label>A: setrobuvir</arm_group_label>
    <arm_group_label>B: setrobuvir + DNV/r</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female adults, 18-65 years of age, inclusive&#xD;
&#xD;
          -  Weight &gt;/= 45.0 kg&#xD;
&#xD;
          -  Body mass index (BMI) 18.0 - 35.0 kg/m2, inclusive&#xD;
&#xD;
          -  Females of childbearing potential and males and their female partners of childbearing&#xD;
             potential must agree to use two forms of non-hormonal contraception as defined by&#xD;
             protocol&#xD;
&#xD;
          -  Subjects with a history of substance abuse may be enrolled provided they have not&#xD;
             abused drugs or alcohol for at least 6 months&#xD;
&#xD;
          -  Healthy subjects only:&#xD;
&#xD;
        Medical history without major recent or ongoing pathology Laboratory values at screening&#xD;
        and Day -1 within the normal range or showing no clinically relevant deviations&#xD;
&#xD;
          -  Subjects with hepatic impairment only:&#xD;
&#xD;
        Stable mild liver disease (Child-Pugh A) of cryptogenic, post-hepatic, hepatitis B/C, or&#xD;
        alcoholic origin Stable hepatic impairment defined as no clinically significant change in&#xD;
        disease status within the last 30 days Must be on stable dose of medication and/or&#xD;
        treatment regimen at least 2 weeks before dosing of study medication&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating women or males with female partners who are pregnant or&#xD;
             lactating&#xD;
&#xD;
          -  Active infection or febrile illness &lt;/= 10 days prior to the first dose of study&#xD;
             medication&#xD;
&#xD;
          -  Uncontrolled/untreated hypertension&#xD;
&#xD;
          -  Inadequate renal function&#xD;
&#xD;
          -  Positive urine drug screen or positive breath alcohol test at screening and on Day -1&#xD;
             of each period&#xD;
&#xD;
          -  An average alcohol intake of more than 2 units per day or 14 units per week until 48&#xD;
             hours prior to enrollment&#xD;
&#xD;
          -  History of any significant drug-related allergy or hepatotoxicity&#xD;
&#xD;
          -  Participation in other clinical studies with an investigational drug or new chemical&#xD;
             entity within 3 months (6 months for biologic therapies) prior to the first dose of&#xD;
             study medication&#xD;
&#xD;
          -  Positive for HIV infection&#xD;
&#xD;
          -  Any clinically significant cardiovascular or cerebrovascular disease&#xD;
&#xD;
          -  Healthy subjects only:&#xD;
&#xD;
        Any clinically significant concomitant disease or condition that could interfere with, or&#xD;
        for which the treatment might interfere with, the conduct of the study, absorption of&#xD;
        medication, or that would, in the opinion of the investigator, pose an unacceptable risk to&#xD;
        the subject in this study Positive screening test for HBsAg or HCV antibody&#xD;
&#xD;
          -  Subjects with hepatic impairment only:&#xD;
&#xD;
        Severe ascites at screening or Day -1 History of or current severe hepatic encephalopathy&#xD;
        (Grade 3 or higher) Biliary liver cirrhosis or other causes of hepatic impairment not&#xD;
        related to parenchymal disorder and/or disease of the liver Positive screening test for HCV&#xD;
        antigen&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Balatonfuered</city>
        <zip>8230</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Budapest</city>
        <zip>1076</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Warszawa</city>
        <zip>01-201</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hungary</country>
    <country>Poland</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>October 23, 2012</study_first_submitted>
  <study_first_submitted_qc>October 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 25, 2012</study_first_posted>
  <last_update_submitted>November 1, 2016</last_update_submitted>
  <last_update_submitted_qc>November 1, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 2, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ritonavir</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/NCT01714154
org study id: NP28326
secondary id: 2012-002283-28
nct id: NCT01714154
lead sponsor: 
This multi-center, fixed-sequence, open-label, multiple-dose, 2-period study will evaluate
      the safety, tolerability and pharmacokinetics of setrobuvir alone or in combination with
      ritonavir-boosted danoprevir in subjects with mild hepatic impairment compared to healthy
      controls. All subjects will receive multiple doses of setrobuvir orally for 10 days in Period
      1 and multiple doses of setrobuvir plus ritonavir-boosted danoprevir orally for 10 days in
      Period 2, with a washout phase of at least 9 days between treatments.
allocation: Non-Randomized
intervention model: Parallel Assignment
masking: None (Open Label)
measure: Safety: Incidence of adverse events
time frame: approximately 40 days
measure: Pharmacokinetics: Maximum plasma concentration at steady-state (Css,max)
time frame: up to 16 days
measure: Pharmacokinetics: Total area under the concentration-time curve form time 0 to 12 hours post-dose at steady-state (AUCss,0-12h)
time frame: up to 16 days
measure: Pharmacokinetics: Plasma concentration at steady-state 12 hours post-dose (Css, 12h)
time frame: up to 16 days
measure: Pharmacokinetics: Time to maximum plasma concentration (tmax)
time frame: up to 16 days
measure: Pharmacokinetics: Elimination half-life (t1/2)
time frame: up to 16 days
measure: Pharmacokinetics: Apparent oral clearance at steady-state (CLss/F)
time frame: up to 16 days
measure: Pharmacokinetics: Cumulative amount excreted at steady-state (Aess)
time frame: up to 16 days
measure: Pharmacokinetics: Fraction of orally administered drug excreted into urine (fe/f)
time frame: up to 16 days
measure: Pharmacokinetics of danoprevir in combination with setrobuvir: Area under the concentration-time curve (AUC)
time frame: up to 12 days
measure: Pharmacokinetics of ritonavir in combination with setrobuvir: Area under the concentration-time curve (AUC)
time frame: up to 12 days
arm group label: A: setrobuvir
arm group type: Experimental
arm group label: B: setrobuvir + DNV/r
arm group type: Experimental
intervention type: Drug
intervention name: danoprevir
description: 100 mg orally every 12 hours
arm group label: B: setrobuvir + DNV/r
intervention type: Drug
intervention name: ritonavir
description: 100 mg orally every 12 hours
arm group label: B: setrobuvir + DNV/r
intervention type: Drug
intervention name: setrobuvir
description: 200 mg orally every 12 hours
arm group label: A: setrobuvir
arm group label: B: setrobuvir + DNV/r
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
facility: 
facility: 
country: Hungary
country: Poland
responsible party type: Sponsor
mesh term: Ritonavir