<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/NCT01678131</url>
  </required_header>
  <id_info>
    <org_study_id>7009-048</org_study_id>
    <secondary_id>2012-003284-21</secondary_id>
    <nct_id>NCT01678131</nct_id>
  </id_info>
  <brief_title>Evaluating Fine Needle Aspiration to Measure Hepatic Vaniprevir (MK-7009) Concentrations in Participants With Chronic Hepatitis C (MK-7009-048)</brief_title>
  <official_title>A Randomized Clinical Trial Using Fine Needle Aspiration For Evaluation of Hepatic Pharmacokinetics of MK-7009 in Chronic Hepatitis C Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the technical feasibility of using fine needle aspiration (FNA) of&#xD;
      liver tissue to obtain vaniprevir (MK-7009) liver pharmacokinetic (PK) data, working towards&#xD;
      identifying a minimally invasive, reproducible platform to measure liver PK. The study will&#xD;
      be done in 2 parts. In Part 1, participants will be randomized to one of five FNA/core needle&#xD;
      biopsy (CNB) time-point collection sequences. In Part 2, participants will be randomized to&#xD;
      one of two possible doses of vaniprevir and will be assigned to one of five FNA/CNB&#xD;
      time-point collection sequences; participants in Part 2 will also receive background therapy&#xD;
      with pegylated interferon alpha-2b (Peg-IFN alpha-2b) and ribavirin (RBV). The primary&#xD;
      hypothesis is that there is a greater than 80% posterior probability that vaniprevir&#xD;
      concentrations are successfully obtained at least 60% of the time from FNA liver samples&#xD;
      collected at 2 of 3 specified timepoints.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 30, 2012</start_date>
  <completion_date type="Actual">September 2, 2013</completion_date>
  <primary_completion_date type="Actual">August 27, 2013</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>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants From Whom Detectable Concentrations of Hepatic Vaniprevir Are Obtained by FNA</measure>
    <time_frame>Day 7 up to Day 10 at 3 of the following timepoints: 3, 12, 24, 48 and 72 hours postdose</time_frame>
    <description>Liver samples were collected by FNA at 3 of 5 of the following specified postdose timepoints: 3, 12, 24, 48 and 72 hours after a single vaniprevir dose on Day 7. The technical success of the FNA procedure was established for a participant if vaniprevir was detected from at least 2 of the 3 FNA collection timepoints.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Chronic Hepatitis C</condition>
  <arm_group>
    <arm_group_label>Vaniprevir 600 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 600 mg vaniprevir only on days 1-7, and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vaniprevir 600 mg + Peg-IFN + RBV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 600 mg vaniprevir on Days 1-7; Peg-IFN alpha-2b once a week, RBV daily from Day 1 up to Day 21; and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vaniprevir 300 mg + Peg-IFN + RBV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 300 mg vaniprevir from Days 1-7; Peg-IFN alpha-2b once a week, RBV daily from Day 1 up to Day 21; and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vaniprevir 600 mg</intervention_name>
    <description>Vaniprevir capsules, were administered orally, twice per day (BID) to achieve a final daily dose of 600 mg on Days 1 through 6; and a single dose of 600 mg, orally, on Day 7.</description>
    <arm_group_label>Vaniprevir 600 mg</arm_group_label>
    <arm_group_label>Vaniprevir 600 mg + Peg-IFN + RBV</arm_group_label>
    <other_name>MK-7009</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Peg-IFN alfa-2b</intervention_name>
    <description>Peg-IFN alfa-2b was administered at 1.5 µg/kg per week by subcutaneous injections on Days 1, 8, 15 and 21</description>
    <arm_group_label>Vaniprevir 300 mg + Peg-IFN + RBV</arm_group_label>
    <arm_group_label>Vaniprevir 600 mg + Peg-IFN + RBV</arm_group_label>
    <other_name>PegIntron™</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ribavirin</intervention_name>
    <description>Ribavirin capsules were administered on Days 1-21, orally, twice daily for a total daily dose of 600 - 1400 mg, depending on the participant's weight</description>
    <arm_group_label>Vaniprevir 300 mg + Peg-IFN + RBV</arm_group_label>
    <arm_group_label>Vaniprevir 600 mg + Peg-IFN + RBV</arm_group_label>
    <other_name>Rebetol™</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Liver samples from FNA</intervention_name>
    <description>Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.</description>
    <arm_group_label>Vaniprevir 300 mg + Peg-IFN + RBV</arm_group_label>
    <arm_group_label>Vaniprevir 600 mg</arm_group_label>
    <arm_group_label>Vaniprevir 600 mg + Peg-IFN + RBV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vaniprevir 300 mg</intervention_name>
    <description>Vaniprevir capsules were administered orally, twice per day to achieve a final daily dose of 300 mg on Days 1 through 6; and a single dose of 300 mg, orally, on Day 7.</description>
    <arm_group_label>Vaniprevir 300 mg + Peg-IFN + RBV</arm_group_label>
    <other_name>MK-7009</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Liver samples from CNB</intervention_name>
    <description>Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.</description>
    <arm_group_label>Vaniprevir 300 mg + Peg-IFN + RBV</arm_group_label>
    <arm_group_label>Vaniprevir 600 mg</arm_group_label>
    <arm_group_label>Vaniprevir 600 mg + Peg-IFN + RBV</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body Mass Index (BMI) ≥18.5 kg/m^2 and ≤32.0 kg/m^2&#xD;
&#xD;
          -  Under evaluation for treatment of chronic hepatitis C virus (HCV)&#xD;
&#xD;
          -  Chronic compensated, genotype 1 HCV infection&#xD;
&#xD;
          -  Treatment-naïve or previously treated and tolerated at least 12 weeks of continuous&#xD;
             licensed interferon (including pegylated interferon) and ribavirin combination therapy&#xD;
             with at least a partial response, or previously treated with investigational products&#xD;
             and/or vaccines, other than HCV nonstructural proteins (NS) NS3/4A protease&#xD;
             inhibitors, either alone or in combination with other licensed therapies&#xD;
&#xD;
          -  Able to avoid use of anticoagulants, nonsteroidal anti-inflammatory agents and aspirin&#xD;
             for at least seven (7) days preceding the initial liver biopsy and continuing&#xD;
             throughout the entire study&#xD;
&#xD;
          -  Female participants of childbearing potential or male participants with female sexual&#xD;
             partners of childbearing potential must agree to use two acceptable methods of birth&#xD;
             control from 2 weeks prior to the first dose through at least 6 months after last dose&#xD;
             of study drug, or longer if dictated by local regulation&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Pregnant, lactating, or intending to become pregnant or donate eggs, or intending to&#xD;
             donate sperm&#xD;
&#xD;
          -  History of stroke, chronic seizures, or major neurological disorder&#xD;
&#xD;
          -  Did not achieve a viral response to prior treatment with licensed interferon-based&#xD;
             therapy&#xD;
&#xD;
          -  Previously treated with an NS3/4A protease inhibitor (investigational or licensed)&#xD;
&#xD;
          -  Evidence or history of chronic hepatitis not caused by HCV infection including but not&#xD;
             limited to non-HCV viral hepatitis, nonalcoholic steatohepatitis (NASH), drug-induced&#xD;
             hepatitis or autoimmune hepatitis&#xD;
&#xD;
          -  Clinical or laboratory evidence of cirrhosis or other advanced liver disease&#xD;
&#xD;
          -  Decompensated liver disease as indicated by a history of ascites, hepatic&#xD;
             encephalopathy, or bleeding esophageal varices&#xD;
&#xD;
          -  Diagnosed with or suspected of having hepatocellular carcinoma&#xD;
&#xD;
          -  Co-infection with human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Positive hepatitis B surface antigen or other evidence of active hepatitis B infection&#xD;
&#xD;
          -  History of gastric bypass surgery or bowel resection&#xD;
&#xD;
          -  History of clinically significant uncontrolled endocrine, gastrointestinal,&#xD;
             cardiovascular, hematological, immunological, renal, respiratory, or genitourinary&#xD;
             abnormalities or diseases&#xD;
&#xD;
          -  History of clinically significant neoplastic disease&#xD;
&#xD;
          -  Consumption of excessive amounts of alcohol, defined as greater than 3 glasses of&#xD;
             alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL], wine [125&#xD;
             mL], or distilled spirits [25 mL]) per day&#xD;
&#xD;
          -  Regular user, including use of any illicit drugs, or has a history of drug (including&#xD;
             alcohol) abuse within the last 3 months&#xD;
&#xD;
          -  Surgery or donation of 1 unit of blood (approximately 500 mL) or participation in&#xD;
             another investigational study within a period of 4 weeks prior to the prestudy&#xD;
             (screening) visit&#xD;
&#xD;
          -  History of multiple and/or severe allergies, or has had an anaphylactic reaction or&#xD;
             intolerability to prescription or nonprescription drugs or food&#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>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <removed_countries>
    <country>Moldova, Republic of</country>
  </removed_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <results_first_submitted>September 26, 2014</results_first_submitted>
  <results_first_submitted_qc>September 26, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">September 29, 2014</results_first_posted>
  <last_update_submitted>August 24, 2022</last_update_submitted>
  <last_update_submitted_qc>August 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis C, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ribavirin</mesh_term>
    <mesh_term>Peginterferon alfa-2b</mesh_term>
    <mesh_term>Interferon alpha-2</mesh_term>
    <mesh_term>Liver Extracts</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_type>CSR Synopsis</doc_type>
      <doc_url>http://www.merck.com/clinical-trials/study.html?id=7009-048&amp;kw=7009-048&amp;tab=access</doc_url>
    </study_doc>
  </study_docs>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>600 mg Vaniprevir</title>
          <description>Participants received 600 mg vaniprevir only from Days 1-7; and had postdose liver biopsy from Day 7 up to Day 10 done by Fine Needle Aspiration (FNA) and Core Needle Biopsy (CNB).</description>
        </group>
        <group group_id="P2">
          <title>300 mg Vaniprevir + PegIFN/RBV</title>
          <description>Participants received 300 mg vaniprevir from Days 1-7; Pegylated Interferon (Peg-IFN) alpha-2b once weekly, Ribavirin (RBV) twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.</description>
        </group>
        <group group_id="P3">
          <title>600 mg Vaniprevir + PegIFN/RBV</title>
          <description>Participants received 600 mg vaniprevir from Days 1-7; Peg-IFN once weekly, RBV twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>600 mg Vaniprevir</title>
          <description>Participants received 600 mg vaniprevir only from Days 1-7; and had postdose liver biopsy from Day 7 up to Day 10 done by Fine Needle Aspiration (FNA) and Core Needle Biopsy (CNB).</description>
        </group>
        <group group_id="B2">
          <title>300 mg Vaniprevir + PegIFN/RBV</title>
          <description>Participants received 300 mg vaniprevir from Days 1-7; Pegylated Interferon (Peg-IFN) alpha-2b once weekly, Ribavirin (RBV) twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.</description>
        </group>
        <group group_id="B3">
          <title>600 mg Vaniprevir + PegIFN/RBV</title>
          <description>Participants received 600 mg vaniprevir from Days 1-7; Peg-IFN once weekly, RBV twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="11"/>
            <count group_id="B4" value="31"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="43.7" spread="10.6"/>
                    <measurement group_id="B2" value="43.9" spread="12.1"/>
                    <measurement group_id="B3" value="38.9" spread="8.0"/>
                    <measurement group_id="B4" value="42.1" spread="10.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants From Whom Detectable Concentrations of Hepatic Vaniprevir Are Obtained by FNA</title>
        <description>Liver samples were collected by FNA at 3 of 5 of the following specified postdose timepoints: 3, 12, 24, 48 and 72 hours after a single vaniprevir dose on Day 7. The technical success of the FNA procedure was established for a participant if vaniprevir was detected from at least 2 of the 3 FNA collection timepoints.</description>
        <time_frame>Day 7 up to Day 10 at 3 of the following timepoints: 3, 12, 24, 48 and 72 hours postdose</time_frame>
        <population>Participants treated with vaniprevir who had hepatic FNA collected at 3 timepoints. One participant from the 300 mg Vaniprevir + Peg-IFN/RBV treatment group, and one participant from the 600 mg Vaniprevir + Peg-IFN/RBV treatment group discontinued treatment prior to collection of 3 FNAs, and were therefore excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>600 mg Vaniprevir</title>
            <description>Participants received 600 mg vaniprevir only from Days 1-7; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.</description>
          </group>
          <group group_id="O2">
            <title>300 mg Vaniprevir + PegIFN/RBV</title>
            <description>Participants received 300 mg vaniprevir from Days 1-7; Pegylated Interferon (Peg-IFN) alpha-2b once weekly, Ribavirin (RBV) twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.</description>
          </group>
          <group group_id="O3">
            <title>600 mg Vaniprevir + PegIFN/RBV</title>
            <description>Participants received 600 mg vaniprevir from Days 1-7; Peg-IFN once weekly, RBV twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants From Whom Detectable Concentrations of Hepatic Vaniprevir Are Obtained by FNA</title>
          <description>Liver samples were collected by FNA at 3 of 5 of the following specified postdose timepoints: 3, 12, 24, 48 and 72 hours after a single vaniprevir dose on Day 7. The technical success of the FNA procedure was established for a participant if vaniprevir was detected from at least 2 of the 3 FNA collection timepoints.</description>
          <population>Participants treated with vaniprevir who had hepatic FNA collected at 3 timepoints. One participant from the 300 mg Vaniprevir + Peg-IFN/RBV treatment group, and one participant from the 600 mg Vaniprevir + Peg-IFN/RBV treatment group discontinued treatment prior to collection of 3 FNAs, and were therefore excluded from the analysis.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The posterior percentage probability of the true success rate of the FNA procedure for the 3 combined treatment groups (n=29) was determined by a Bayesian calculation, using a Jeffrey's prior distribution (i.e. Beta [0.5,0.5]) on the true success rate. Neither P-values, nor confidence intervals are estimated in this analysis. The primary hypothesis was met if the posterior percentage probability was &gt; 80% that the true success rate is at least 60%.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <param_type>Posterior Percentage Probability</param_type>
            <param_value>100</param_value>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>up to 14 days after last treatment with vaniprevir (up to approximately Day 21)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>600 mg Vaniprevir</title>
          <description>Participants received 600 mg vaniprevir only from Days 1-7; and had postdose liver biopsy from Day 7 up to Day 10 done by Fine Needle Aspiration (FNA) and Core Needle Biopsy (CNB).</description>
        </group>
        <group group_id="E2">
          <title>300 mg Vaniprevir + PegIFN/RBV</title>
          <description>Participants received 300 mg vaniprevir from Days 1-7; Pegylated Interferon (Peg-IFN) alpha-2b once weekly, Ribavirin (RBV) twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.</description>
        </group>
        <group group_id="E3">
          <title>600 mg Vaniprevir + PegIFN/RBV</title>
          <description>Participants received 600 mg vaniprevir from Days 1-7; Peg-IFN once weekly, RBV twice daily from Day 1 up to Day 21; and had postdose liver biopsy from Day 7 up to Day 10 done by FNA and CNB.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA Version 16.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Epigastric pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Loose stools</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="17" subjects_affected="10" subjects_at_risk="10"/>
                <counts group_id="E3" events="10" subjects_affected="8" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Rigors</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="6" subjects_affected="5" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tonic convulsion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme LLC</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01678131
org study id: 7009-048
secondary id: 2012-003284-21
nct id: NCT01678131
lead sponsor: 
has dmc: No
This study will evaluate the technical feasibility of using fine needle aspiration (FNA) of
      liver tissue to obtain vaniprevir (MK-7009) liver pharmacokinetic (PK) data, working towards
      identifying a minimally invasive, reproducible platform to measure liver PK. The study will
      be done in 2 parts. In Part 1, participants will be randomized to one of five FNA/core needle
      biopsy (CNB) time-point collection sequences. In Part 2, participants will be randomized to
      one of two possible doses of vaniprevir and will be assigned to one of five FNA/CNB
      time-point collection sequences; participants in Part 2 will also receive background therapy
      with pegylated interferon alpha-2b (Peg-IFN alpha-2b) and ribavirin (RBV). The primary
      hypothesis is that there is a greater than 80% posterior probability that vaniprevir
      concentrations are successfully obtained at least 60% of the time from FNA liver samples
      collected at 2 of 3 specified timepoints.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Number of Participants From Whom Detectable Concentrations of Hepatic Vaniprevir Are Obtained by FNA
time frame: Day 7 up to Day 10 at 3 of the following timepoints: 3, 12, 24, 48 and 72 hours postdose
description: Liver samples were collected by FNA at 3 of 5 of the following specified postdose timepoints: 3, 12, 24, 48 and 72 hours after a single vaniprevir dose on Day 7. The technical success of the FNA procedure was established for a participant if vaniprevir was detected from at least 2 of the 3 FNA collection timepoints.
arm group label: Vaniprevir 600 mg
arm group type: Experimental
description: Participants received 600 mg vaniprevir only on days 1-7, and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10.
arm group label: Vaniprevir 600 mg + Peg-IFN + RBV
arm group type: Experimental
description: Participants received 600 mg vaniprevir on Days 1-7; Peg-IFN alpha-2b once a week, RBV daily from Day 1 up to Day 21; and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10.
arm group label: Vaniprevir 300 mg + Peg-IFN + RBV
arm group type: Experimental
description: Participants received 300 mg vaniprevir from Days 1-7; Peg-IFN alpha-2b once a week, RBV daily from Day 1 up to Day 21; and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10.
intervention type: Drug
intervention name: Vaniprevir 600 mg
description: Vaniprevir capsules, were administered orally, twice per day (BID) to achieve a final daily dose of 600 mg on Days 1 through 6; and a single dose of 600 mg, orally, on Day 7.
arm group label: Vaniprevir 600 mg
arm group label: Vaniprevir 600 mg + Peg-IFN + RBV
other name: MK-7009
intervention type: Biological
intervention name: Peg-IFN alfa-2b
description: Peg-IFN alfa-2b was administered at 1.5 µg/kg per week by subcutaneous injections on Days 1, 8, 15 and 21
arm group label: Vaniprevir 300 mg + Peg-IFN + RBV
arm group label: Vaniprevir 600 mg + Peg-IFN + RBV
other name: PegIntron™
intervention type: Biological
intervention name: Ribavirin
description: Ribavirin capsules were administered on Days 1-21, orally, twice daily for a total daily dose of 600 - 1400 mg, depending on the participant's weight
arm group label: Vaniprevir 300 mg + Peg-IFN + RBV
arm group label: Vaniprevir 600 mg + Peg-IFN + RBV
other name: Rebetol™
intervention type: Procedure
intervention name: Liver samples from FNA
description: Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.
arm group label: Vaniprevir 300 mg + Peg-IFN + RBV
arm group label: Vaniprevir 600 mg
arm group label: Vaniprevir 600 mg + Peg-IFN + RBV
intervention type: Drug
intervention name: Vaniprevir 300 mg
description: Vaniprevir capsules were administered orally, twice per day to achieve a final daily dose of 300 mg on Days 1 through 6; and a single dose of 300 mg, orally, on Day 7.
arm group label: Vaniprevir 300 mg + Peg-IFN + RBV
other name: MK-7009
intervention type: Procedure
intervention name: Liver samples from CNB
description: Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.
arm group label: Vaniprevir 300 mg + Peg-IFN + RBV
arm group label: Vaniprevir 600 mg
arm group label: Vaniprevir 600 mg + Peg-IFN + RBV
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
country: Moldova, Republic of
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis C, Chronic
mesh term: Hepatitis
mesh term: Hepatitis, Chronic
mesh term: Ribavirin
mesh term: Peginterferon alfa-2b
mesh term: Interferon alpha-2
mesh term: Liver Extracts
sharing ipd: Yes
ipd description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
study doc: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 