<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/NCT02219685</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-337-1445</org_study_id>
    <nct_id>NCT02219685</nct_id>
  </id_info>
  <brief_title>Ledipasvir/Sofosbuvir Fixed-Dose Combination on Cerebral Metabolism and Neurocognition in Treatment-Naive and Treatment-Experienced Participants With Chronic Genotype 1 HCV Infection</brief_title>
  <official_title>A Phase 2, Single-Center, Double-Blind, Placebo-Controlled, Randomized Study to Investigate the Effect of Ledipasvir/Sofosbuvir Fixed-Dose Combination on Cerebral Metabolism and Neurocognition in Treatment-Naive and Treatment-Experienced Subjects With Chronic Genotype 1 HCV Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gilead Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objectives of this study are to evaluate the effect of sustained virologic&#xD;
      response (SVR) on cerebral metabolism as determined by magnetic resonance spectroscopy (MRS)&#xD;
      and on neurocognition as measured by neurocognitive tests. This study will also evaluate the&#xD;
      antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose&#xD;
      combination (FDC) for 12 weeks in treatment-naive or treatment-experienced adults.&#xD;
&#xD;
      During the blinded treatment phase, participants will be randomized 2:1 to receive LDV/SOF&#xD;
      FDC or placebo for 12 weeks. After the unblinding at the Posttreatment Week 4 visit,&#xD;
      participants in the placebo group will be offered open-label treatment of LDV/SOF FDC for 12&#xD;
      weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">August 2015</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG</measure>
    <time_frame>Baseline; Posttreatment Week 4</time_frame>
    <description>MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal N-acetylaspartate (NAA) + N-acetylaspartylglutamate (NAAG) was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline</measure>
    <time_frame>Baseline; Posttreatment Week 4</time_frame>
    <description>MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal choline was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol</measure>
    <time_frame>Baseline; Posttreatment Week 4</time_frame>
    <description>MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal myoinositol was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score</measure>
    <time_frame>Baseline; Posttreatment Week 4</time_frame>
    <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).&#xD;
For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Attention Scaled Score</measure>
    <time_frame>Baseline; Posttreatment Week 4</time_frame>
    <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).&#xD;
For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed</measure>
    <time_frame>Baseline; Posttreatment Week 4</time_frame>
    <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).&#xD;
For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation</measure>
    <time_frame>Baseline; Posttreatment Week 4</time_frame>
    <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age &amp; education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).&#xD;
For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Motor</measure>
    <time_frame>Baseline; Posttreatment Week 4</time_frame>
    <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).&#xD;
For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)</measure>
    <time_frame>Posttreatment Weeks 4, 12, and 24</time_frame>
    <description>SVR4, SVR12, and SVR24 were defined as HCV RNA &lt; the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 4, 12, and 24 weeks after stopping study treatment with LDV/SOF, respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score</measure>
    <time_frame>Baseline; Posttreatment Week 24</time_frame>
    <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).&#xD;
For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Attention Scaled Score</measure>
    <time_frame>Baseline; Posttreatment Week 24</time_frame>
    <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).&#xD;
For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed</measure>
    <time_frame>Baseline; Posttreatment Week 24</time_frame>
    <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).&#xD;
For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation</measure>
    <time_frame>Baseline; Posttreatment Week 24</time_frame>
    <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age &amp; education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).&#xD;
For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Motor</measure>
    <time_frame>Baseline; Posttreatment Week 24</time_frame>
    <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).&#xD;
For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Short Form 36 (SF-36) Health Survey Scale - Physical Component Score</measure>
    <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
    <description>The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The first 6 concepts constitute the physical component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower scores representing more disability and higher scores representing less disability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by SF-36 Health Survey Scale - Mental Component Score</measure>
    <time_frame>Baseline; Posttreatment (PT) Weeks 4 and 24</time_frame>
    <description>The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The last 5 concepts constitute the mental component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower score representing more disability and higher scores representing less disability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Chronic Liver Disease Questionnaire - HCV (CLDQ-HCV)</measure>
    <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
    <description>The CLDQ-HCV is a disease-specific questionnaire measuring health-related quality of life. CLDQ-HCV scores are calculated using participant responses to 29 questions divided into 4 domains: Activity/Energy, Emotion, Worry, and Systemic. An overall CLDQ-HCV score is calculated by taking the mean of all domain scores. Overall CLDQ-HCV scores range between 1 and 7, with higher scores representing better quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)</measure>
    <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
    <description>The FACIT-Fatigue score was measured using a 40-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale from 0 (Not at all) to 4 (Very much). The FACIT-F total score was calculated by taking the sum of all 40 individual scores and ranged from 0-160, with higher scores indicating better quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Work Productivity and Activity Impairment Questionnaire, Hepatitis C (WPAI: Hepatitis C) - Overall Work Impairment</measure>
    <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
    <description>Impairment in overall work productivity was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall work impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from working).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by WPAI: Hepatitis C - Activity Impairment</measure>
    <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
    <description>Activity impairment was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall activity impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from performing regular activities).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Pre-treatment Assessment in Mood Related Assessment at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Beck Depression Inventory-II (BDI-II)</measure>
    <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
    <description>The BDI-II is a 21-item self-report instrument for measuring the severity of depression. Each item is rated on a 4-point scale ranging from 0 to 3. The item scores are summed to yield a derived total score that can range from 0 to 63 with lower values indicating less depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Pre-treatment Assessment in Mood Related Assessment at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Beck Hopelessness Scale (BHS)</measure>
    <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
    <description>The BHS is a 20-item scale for measuring the extent of negative attitudes about the future (pessimism) as perceived by adolescents and adults. The BHS consists of 20 true-false statements. Each of the 20 statements is scored 1 or 0. Of the 20 true-false statements, 9 are keyed FALSE, and 11 are keyed TRUE to indicate endorsement of pessimism about the future. The item scores are summed to yield a total score that can range from 0 to 20 with higher scores indicating greater hopelessness.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Hepatitis C Virus Infection</condition>
  <arm_group>
    <arm_group_label>LDV/SOF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive LDV/SOF FDC for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive LDV/SOF placebo for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Open-Label Treatment Phase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Following Posttreatment Week 4, participants in the placebo group will be offered open-label treatment with LDV/SOF FDC for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LDV/SOF</intervention_name>
    <description>90/400 mg FDC tablet administered orally once daily</description>
    <arm_group_label>LDV/SOF</arm_group_label>
    <arm_group_label>Open-Label Treatment Phase</arm_group_label>
    <other_name>Harvoni®</other_name>
    <other_name>GS-5885/GS-7977</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Tablet administered orally once daily</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy&#xD;
&#xD;
          -  Chronic genotype 1 HCV infection&#xD;
&#xD;
          -  Screening laboratory values within defined thresholds&#xD;
&#xD;
          -  Use of protocol-specified method(s) of contraception if female of childbearing&#xD;
             potential or sexually active male&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically-significant illness (other than HCV) or any other major medical disorder&#xD;
             that may interfere with treatment, assessment, or compliance with the protocol.&#xD;
             Current or prior history of any of the following:&#xD;
&#xD;
               -  Hepatic decompensation&#xD;
&#xD;
               -  Solid organ transplantation&#xD;
&#xD;
               -  Significant pulmonary or cardiac disease&#xD;
&#xD;
               -  Chronic liver disease of a non-HCV etiology&#xD;
&#xD;
               -  Hepatocellular carcinoma (HCC)&#xD;
&#xD;
               -  Infection with hepatitis B virus (HBV)&#xD;
&#xD;
               -  Infection with human immunodeficiency virus (HIV)&#xD;
&#xD;
               -  History of recent epilepsy (within 2 years of screening) or cerebral vascular&#xD;
                  accident (CVA)&#xD;
&#xD;
               -  Structural brain damage&#xD;
&#xD;
          -  Presence of cirrhosis&#xD;
&#xD;
          -  Contraindication to MRI&#xD;
&#xD;
          -  Pregnant or nursing female&#xD;
&#xD;
          -  Prior treatment NS5A directly-acting antiviral agent. Any interferon (IFN)-containing&#xD;
             regimen within 8 weeks of Screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Benedetta Massetto, MD</last_name>
    <role>Study Director</role>
    <affiliation>Gilead Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>August 15, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 19, 2014</study_first_posted>
  <results_first_submitted>August 2, 2016</results_first_submitted>
  <results_first_submitted_qc>October 7, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">November 30, 2016</results_first_posted>
  <last_update_submitted>October 19, 2018</last_update_submitted>
  <last_update_submitted_qc>October 19, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 16, 2018</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>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sofosbuvir</mesh_term>
    <mesh_term>Ledipasvir, sofosbuvir drug combination</mesh_term>
    <mesh_term>Ledipasvir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>18 months after study completion</ipd_time_frame>
    <ipd_access_criteria>A secured external environment with username, password, and RSA code.</ipd_access_criteria>
    <ipd_url>http://www.gilead.com/research/disclosure-and-transparency</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at 1 study site in the United States. The first participant was screened on 25 August 2014. The last study visit occurred on 07 April 2016.</recruitment_details>
      <pre_assignment_details>54 participants were screened.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>LDV/SOF</title>
          <description>Ledipasvir/sofosbuvir (LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet once daily for 12 weeks</description>
        </group>
        <group group_id="P2">
          <title>Placebo, Followed by Open-Label LDV/SOF</title>
          <description>LDV/SOF placebo tablet once daily for 12 weeks, followed by LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Blinded Treatment Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrew Consent</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Open-Label (After Posttreatment Week 4)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0">Only participants from the Placebo arm were eligible to enroll in the Open-Label Phase.</participants>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>LDV/SOF</title>
          <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>LDV/SOF placebo tablet once daily for 12 weeks, followed by LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks</description>
        </group>
        <group group_id="B3">
          <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="26"/>
            <count group_id="B2" value="14"/>
            <count group_id="B3" value="40"/>
          </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="44" spread="12.4"/>
                    <measurement group_id="B2" value="47" spread="9.8"/>
                    <measurement group_id="B3" value="45" spread="11.5"/>
                  </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="12"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior HCV Treatment Experience</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Treatment-Naive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment-Experienced</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HCV Genotype</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Genotype 1a</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Genotype 1b</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>IL28B Status</title>
          <description>The CC, CT, and TT alleles are different forms of the IL28b gene.</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>CC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HCV RNA</title>
          <units>log10 IU/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.2" spread="0.57"/>
                    <measurement group_id="B2" value="6.4" spread="0.62"/>
                    <measurement group_id="B3" value="6.3" spread="0.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HCV RNA Category</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt; 800,000 IU/mL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>≥ 800,000 IU/mL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG</title>
        <description>MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal N-acetylaspartate (NAA) + N-acetylaspartylglutamate (NAAG) was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.</description>
        <time_frame>Baseline; Posttreatment Week 4</time_frame>
        <population>Full Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG</title>
          <description>MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal N-acetylaspartate (NAA) + N-acetylaspartylglutamate (NAAG) was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.</description>
          <population>Full Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug.</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Basal Ganglia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="0.085"/>
                    <measurement group_id="O2" value="-0.01" spread="0.147"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Frontal Cortex</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="0.201"/>
                    <measurement group_id="O2" value="-0.09" spread="0.279"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dorsolateral Prefrontal Cortex</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.154"/>
                    <measurement group_id="O2" value="-0.01" spread="0.142"/>
                  </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_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.58</p_value>
            <p_value_desc>This p-value for treatment effect on basal ganglia was based on a two sample t-test assuming equal variances.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.48</p_value>
            <p_value_desc>This p-value for treatment effect on frontal cortex was based on a two sample t-test assuming equal variances.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.96</p_value>
            <p_value_desc>This p-value for treatment effect on dorsolateral prefrontal cortex was based on a two sample t-test assuming equal variances.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline</title>
        <description>MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal choline was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.</description>
        <time_frame>Baseline; Posttreatment Week 4</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline</title>
          <description>MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal choline was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.</description>
          <population>Full Analysis Set</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Basal Ganglia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.01" spread="0.020"/>
                    <measurement group_id="O2" value="0.00" spread="0.029"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Frontal Cortex</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.01" spread="0.033"/>
                    <measurement group_id="O2" value="0.00" spread="0.055"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dorsolateral Prefrontal Cortex</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.029"/>
                    <measurement group_id="O2" value="0.01" spread="0.023"/>
                  </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_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.54</p_value>
            <p_value_desc>This p-value for treatment effect on basal ganglia was based on a two sample t-test assuming equal variances.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.57</p_value>
            <p_value_desc>This p-value for treatment effect on frontal cortex was based on a two sample t-test assuming equal variances.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.63</p_value>
            <p_value_desc>This p-value for treatment effect on dorsolateral prefrontal cortex was based on a two sample t-test assuming equal variances.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol</title>
        <description>MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal myoinositol was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.</description>
        <time_frame>Baseline; Posttreatment Week 4</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol</title>
          <description>MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal myoinositol was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.</description>
          <population>Full Analysis Set</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Basal Ganglia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.02" spread="0.110"/>
                    <measurement group_id="O2" value="0.00" spread="0.157"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Frontal Cortex</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.01" spread="0.207"/>
                    <measurement group_id="O2" value="0.08" spread="0.156"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dorsolateral Prefrontal Cortex</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.02" spread="0.112"/>
                    <measurement group_id="O2" value="0.00" spread="0.104"/>
                  </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_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.70</p_value>
            <p_value_desc>This p-value for treatment effect on basal ganglia was based on a two sample t-test assuming equal variances.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.21</p_value>
            <p_value_desc>This p-value for treatment effect on frontal cortex was based on a two sample t-test assuming equal variances.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.59</p_value>
            <p_value_desc>This p-value for treatment effect on dorsolateral prefrontal cortex was based on a two sample t-test assuming equal variances.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score</title>
        <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).&#xD;
For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.</description>
        <time_frame>Baseline; Posttreatment Week 4</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score</title>
          <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).&#xD;
For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.</description>
          <population>Full Analysis Set</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.88" spread="19.15"/>
                    <measurement group_id="O2" value="7.93" spread="23.63"/>
                  </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_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0795</p_value>
            <p_value_desc>The p-value was from ANCOVA model for change from baseline with treatment group and baseline as covariates.</p_value_desc>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Attention Scaled Score</title>
        <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).&#xD;
For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.</description>
        <time_frame>Baseline; Posttreatment Week 4</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Attention Scaled Score</title>
          <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).&#xD;
For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.</description>
          <population>Full Analysis Set</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.73" spread="4.29"/>
                    <measurement group_id="O2" value="1.43" spread="3.34"/>
                  </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_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.7007</p_value>
            <p_value_desc>The p-value was from ANCOVA model for change from baseline with treatment group and baseline as covariates.</p_value_desc>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed</title>
        <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).&#xD;
For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.</description>
        <time_frame>Baseline; Posttreatment Week 4</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed</title>
          <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).&#xD;
For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.</description>
          <population>Full Analysis Set</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.96" spread="5.71"/>
                    <measurement group_id="O2" value="4.00" spread="7.27"/>
                  </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_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2677</p_value>
            <p_value_desc>The p-value was ANCOVA model for change from baseline with treatment group and baseline as covariates.</p_value_desc>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation</title>
        <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age &amp; education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).&#xD;
For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.</description>
        <time_frame>Baseline; Posttreatment Week 4</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation</title>
          <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age &amp; education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).&#xD;
For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.</description>
          <population>Full Analysis Set</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.04" spread="21.03"/>
                    <measurement group_id="O2" value="-12.43" spread="15.38"/>
                  </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_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.9870</p_value>
            <p_value_desc>The p-value was from ANCOVA model for change from baseline with treatment group and baseline as covariates.</p_value_desc>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Motor</title>
        <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).&#xD;
For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.</description>
        <time_frame>Baseline; Posttreatment Week 4</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Motor</title>
          <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).&#xD;
For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.</description>
          <population>Full Analysis Set</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.00" spread="17.47"/>
                    <measurement group_id="O2" value="-6.00" spread="17.16"/>
                  </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_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.3388</p_value>
            <p_value_desc>The p-value was from ANCOVA model for change from baseline with treatment group and baseline as covariates.</p_value_desc>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)</title>
        <description>SVR4, SVR12, and SVR24 were defined as HCV RNA &lt; the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 4, 12, and 24 weeks after stopping study treatment with LDV/SOF, respectively.</description>
        <time_frame>Posttreatment Weeks 4, 12, and 24</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Open-Label Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Open-Label Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)</title>
          <description>SVR4, SVR12, and SVR24 were defined as HCV RNA &lt; the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 4, 12, and 24 weeks after stopping study treatment with LDV/SOF, respectively.</description>
          <population>Full Analysis Set</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SVR4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.2" lower_limit="80.4" upper_limit="99.9"/>
                    <measurement group_id="O2" value="100.0" lower_limit="76.8" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SVR12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.3" lower_limit="74.9" upper_limit="99.1"/>
                    <measurement group_id="O2" value="100.0" lower_limit="76.8" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SVR24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.3" lower_limit="74.9" upper_limit="99.1"/>
                    <measurement group_id="O2" value="100.0" lower_limit="76.8" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score</title>
        <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).&#xD;
For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.</description>
        <time_frame>Baseline; Posttreatment Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed. Data for the &quot;Open-Label Phase: LDV/SOF&quot; group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score</title>
          <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).&#xD;
For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed. Data for the &quot;Open-Label Phase: LDV/SOF&quot; group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.42" spread="31.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Attention Scaled Score</title>
        <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).&#xD;
For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.</description>
        <time_frame>Baseline; Posttreatment Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed. Data for the &quot;Open-Label Phase: LDV/SOF&quot; group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Attention Scaled Score</title>
          <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).&#xD;
For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed. Data for the &quot;Open-Label Phase: LDV/SOF&quot; group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.42" spread="0.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed</title>
        <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).&#xD;
For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.</description>
        <time_frame>Baseline; Posttreatment Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed. Data for the &quot;Open-Label Phase: LDV/SOF&quot; group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed</title>
          <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).&#xD;
For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed. Data for the &quot;Open-Label Phase: LDV/SOF&quot; group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.00" spread="7.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation</title>
        <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age &amp; education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).&#xD;
For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.</description>
        <time_frame>Baseline; Posttreatment Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed. Data for the &quot;Open-Label Phase: LDV/SOF&quot; group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation</title>
          <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age &amp; education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).&#xD;
For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed. Data for the &quot;Open-Label Phase: LDV/SOF&quot; group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.67" spread="35.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Motor</title>
        <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).&#xD;
For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.</description>
        <time_frame>Baseline; Posttreatment Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed. Data for the &quot;Open-Label Phase: LDV/SOF&quot; group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Motor</title>
          <description>Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).&#xD;
For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed. Data for the &quot;Open-Label Phase: LDV/SOF&quot; group are not presented because this group did not have a Posttreatment Week 24 visit after receiving placebo. These participants were enrolled into the Open-Label Phase after Posttreatment Week 4.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.21" spread="17.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Short Form 36 (SF-36) Health Survey Scale - Physical Component Score</title>
        <description>The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The first 6 concepts constitute the physical component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower scores representing more disability and higher scores representing less disability.</description>
        <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Short Form 36 (SF-36) Health Survey Scale - Physical Component Score</title>
          <description>The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The first 6 concepts constitute the physical component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower scores representing more disability and higher scores representing less disability.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (LDV/SOF: N =25; Placebo: N =14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.8" spread="5.51"/>
                    <measurement group_id="O2" value="56.2" spread="4.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at PT Wk 4 (LDV/SOF: N =25; Placebo: N =14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="3.73"/>
                    <measurement group_id="O2" value="-0.1" spread="4.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at PT Wk 24 (LDV/SOF: N =23; Placebo: NA)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="4.13"/>
                    <measurement group_id="O2" value="NA" spread="NA">Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by SF-36 Health Survey Scale - Mental Component Score</title>
        <description>The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The last 5 concepts constitute the mental component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower score representing more disability and higher scores representing less disability.</description>
        <time_frame>Baseline; Posttreatment (PT) Weeks 4 and 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by SF-36 Health Survey Scale - Mental Component Score</title>
          <description>The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The last 5 concepts constitute the mental component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower score representing more disability and higher scores representing less disability.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (LDV/SOF: N = 25; Placebo: N = 14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.5" spread="6.25"/>
                    <measurement group_id="O2" value="50.9" spread="10.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at PT Wk 4 (LDV/SOF: N =25; Placebo: N =14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" spread="4.86"/>
                    <measurement group_id="O2" value="-2.9" spread="9.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at PT Wk 24 (LDV/SOF: N =23; Placebo: NA)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" spread="5.77"/>
                    <measurement group_id="O2" value="NA" spread="NA">Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Chronic Liver Disease Questionnaire - HCV (CLDQ-HCV)</title>
        <description>The CLDQ-HCV is a disease-specific questionnaire measuring health-related quality of life. CLDQ-HCV scores are calculated using participant responses to 29 questions divided into 4 domains: Activity/Energy, Emotion, Worry, and Systemic. An overall CLDQ-HCV score is calculated by taking the mean of all domain scores. Overall CLDQ-HCV scores range between 1 and 7, with higher scores representing better quality of life.</description>
        <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Chronic Liver Disease Questionnaire - HCV (CLDQ-HCV)</title>
          <description>The CLDQ-HCV is a disease-specific questionnaire measuring health-related quality of life. CLDQ-HCV scores are calculated using participant responses to 29 questions divided into 4 domains: Activity/Energy, Emotion, Worry, and Systemic. An overall CLDQ-HCV score is calculated by taking the mean of all domain scores. Overall CLDQ-HCV scores range between 1 and 7, with higher scores representing better quality of life.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (LVD/SOF: N =26; Placebo: N =14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.8" spread="0.89"/>
                    <measurement group_id="O2" value="6.0" spread="0.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at PT Wk 4 (LVD/SOF: N =26; Placebo: N =14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="0.61"/>
                    <measurement group_id="O2" value="-0.1" spread="0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at PT Wk 24 (LVD/SOF: N =24; Placebo: NA)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="0.77"/>
                    <measurement group_id="O2" value="NA" spread="NA">Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)</title>
        <description>The FACIT-Fatigue score was measured using a 40-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale from 0 (Not at all) to 4 (Very much). The FACIT-F total score was calculated by taking the sum of all 40 individual scores and ranged from 0-160, with higher scores indicating better quality of life.</description>
        <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)</title>
          <description>The FACIT-Fatigue score was measured using a 40-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale from 0 (Not at all) to 4 (Very much). The FACIT-F total score was calculated by taking the sum of all 40 individual scores and ranged from 0-160, with higher scores indicating better quality of life.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (LDV/SOF: N =26; Placebo: N =14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94.7" spread="12.12"/>
                    <measurement group_id="O2" value="97.0" spread="8.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at PT Wk 4 (LDV/SOF: N =26; Placebo: N =14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1" spread="8.43"/>
                    <measurement group_id="O2" value="-4.4" spread="9.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at PT Wk 24 (LDV/SOF: N =24; Placebo: NA)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.9" spread="9.04"/>
                    <measurement group_id="O2" value="NA" spread="NA">Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Work Productivity and Activity Impairment Questionnaire, Hepatitis C (WPAI: Hepatitis C) - Overall Work Impairment</title>
        <description>Impairment in overall work productivity was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall work impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from working).</description>
        <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Work Productivity and Activity Impairment Questionnaire, Hepatitis C (WPAI: Hepatitis C) - Overall Work Impairment</title>
          <description>Impairment in overall work productivity was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall work impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from working).</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (LDV/SOF: N =24; Placebo: N =10)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.6" spread="28.16"/>
                    <measurement group_id="O2" value="4.0" spread="9.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at PT Wk 4 (LDV/SOF: N =21; Placebo: N =10)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.5" spread="27.31"/>
                    <measurement group_id="O2" value="13.0" spread="22.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at PT Wk 24 (LDV/SOF: N =20; Placebo: NA)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.6" spread="34.01"/>
                    <measurement group_id="O2" value="NA" spread="NA">Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by WPAI: Hepatitis C - Activity Impairment</title>
        <description>Activity impairment was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall activity impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from performing regular activities).</description>
        <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by WPAI: Hepatitis C - Activity Impairment</title>
          <description>Activity impairment was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall activity impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from performing regular activities).</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (LDV/SOF: N =26; Placebo: N =13)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.0" spread="24.17"/>
                    <measurement group_id="O2" value="2.3" spread="8.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at PT Wk 4 (LDV/SOF: N =26; Placebo: N =13)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.9" spread="23.28"/>
                    <measurement group_id="O2" value="6.9" spread="11.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at PT Wk 24 (LDV/SOF: N =20; Placebo: NA)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.1" spread="19.48"/>
                    <measurement group_id="O2" value="NA" spread="NA">Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Pre-treatment Assessment in Mood Related Assessment at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Beck Depression Inventory-II (BDI-II)</title>
        <description>The BDI-II is a 21-item self-report instrument for measuring the severity of depression. Each item is rated on a 4-point scale ranging from 0 to 3. The item scores are summed to yield a derived total score that can range from 0 to 63 with lower values indicating less depression.</description>
        <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Pre-treatment Assessment in Mood Related Assessment at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Beck Depression Inventory-II (BDI-II)</title>
          <description>The BDI-II is a 21-item self-report instrument for measuring the severity of depression. Each item is rated on a 4-point scale ranging from 0 to 3. The item scores are summed to yield a derived total score that can range from 0 to 63 with lower values indicating less depression.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.20" spread="4.73"/>
                    <measurement group_id="O2" value="4.29" spread="5.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Posttreatment Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.40" spread="3.77"/>
                    <measurement group_id="O2" value="0.29" spread="5.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Posttreatment Week 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.74" spread="3.95"/>
                    <measurement group_id="O2" value="NA" spread="NA">Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Pre-treatment Assessment in Mood Related Assessment at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Beck Hopelessness Scale (BHS)</title>
        <description>The BHS is a 20-item scale for measuring the extent of negative attitudes about the future (pessimism) as perceived by adolescents and adults. The BHS consists of 20 true-false statements. Each of the 20 statements is scored 1 or 0. Of the 20 true-false statements, 9 are keyed FALSE, and 11 are keyed TRUE to indicate endorsement of pessimism about the future. The item scores are summed to yield a total score that can range from 0 to 20 with higher scores indicating greater hopelessness.</description>
        <time_frame>Baseline; Posttreatment Weeks 4 and 24</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Blinded Phase: LDV/SOF</title>
            <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
          <group group_id="O2">
            <title>Blinded Phase: Placebo</title>
            <description>LDV/SOF placebo tablet once daily for 12 weeks during the Blinded Treatment Phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Pre-treatment Assessment in Mood Related Assessment at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Beck Hopelessness Scale (BHS)</title>
          <description>The BHS is a 20-item scale for measuring the extent of negative attitudes about the future (pessimism) as perceived by adolescents and adults. The BHS consists of 20 true-false statements. Each of the 20 statements is scored 1 or 0. Of the 20 true-false statements, 9 are keyed FALSE, and 11 are keyed TRUE to indicate endorsement of pessimism about the future. The item scores are summed to yield a total score that can range from 0 to 20 with higher scores indicating greater hopelessness.</description>
          <population>Full Analysis Set</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.27" spread="1.40"/>
                    <measurement group_id="O2" value="1.36" spread="1.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Posttreatment Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.04" spread="1.43"/>
                    <measurement group_id="O2" value="0.14" spread="1.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Posttreatment Week 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.04" spread="0.91"/>
                    <measurement group_id="O2" value="NA" spread="NA">Participants in the Placebo group did not have a Posttreatment Week 24 visit because they were enrolled into the Open-Label Phase after Posttreatment Week 4.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Blinded Treatment Phase: Up to 12 weeks plus 30 days; Open-Label Treatment Phase: Up to 12 weeks plus 30 days</time_frame>
      <desc>Safety Analysis Set</desc>
      <group_list>
        <group group_id="E1">
          <title>LDV/SOF (Blinded Phase)</title>
          <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks</description>
        </group>
        <group group_id="E2">
          <title>Placebo (Blinded Phase)</title>
          <description>LDV/SOF placebo tablet once daily for 12 weeks</description>
        </group>
        <group group_id="E3">
          <title>LDV/SOF (Open-Label Phase), Following Placebo in Blinded Phase</title>
          <description>LDV/SOF (90/400 mg) FDC tablet once daily for 12 weeks during the Open-Label Treatment Phase</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="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 18.1</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="20" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Faeces pale</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Disturbance in attention</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Restless legs syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Orchitis noninfective</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Tooth extraction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </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>After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:&#xD;
The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or&#xD;
The study has been completed at all study sites for at least 2 years</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Trial Disclosures</name_or_title>
      <organization>Gilead Sciences</organization>
      <email>ClinicalTrialDisclosures@gilead.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/NCT02219685
org study id: GS-US-337-1445
nct id: NCT02219685
lead sponsor: 
has dmc: Yes
The primary objectives of this study are to evaluate the effect of sustained virologic
      response (SVR) on cerebral metabolism as determined by magnetic resonance spectroscopy (MRS)
      and on neurocognition as measured by neurocognitive tests. This study will also evaluate the
      antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose
      combination (FDC) for 12 weeks in treatment-naive or treatment-experienced adults.

      During the blinded treatment phase, participants will be randomized 2:1 to receive LDV/SOF
      FDC or placebo for 12 weeks. After the unblinding at the Posttreatment Week 4 visit,
      participants in the placebo group will be offered open-label treatment of LDV/SOF FDC for 12
      weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG
time frame: Baseline; Posttreatment Week 4
description: MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal N-acetylaspartate (NAA) + N-acetylaspartylglutamate (NAAG) was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
measure: Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline
time frame: Baseline; Posttreatment Week 4
description: MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal choline was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
measure: Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol
time frame: Baseline; Posttreatment Week 4
description: MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal myoinositol was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
measure: Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score
time frame: Baseline; Posttreatment Week 4
description: Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).
For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.
measure: Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Attention Scaled Score
time frame: Baseline; Posttreatment Week 4
description: Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).
For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.
measure: Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
time frame: Baseline; Posttreatment Week 4
description: Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).
For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.
measure: Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
time frame: Baseline; Posttreatment Week 4
description: Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age & education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).
For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.
measure: Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Motor
time frame: Baseline; Posttreatment Week 4
description: Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).
For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.
measure: Percentage of Participants With Sustained Virologic Response (SVR) at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)
time frame: Posttreatment Weeks 4, 12, and 24
description: SVR4, SVR12, and SVR24 were defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 4, 12, and 24 weeks after stopping study treatment with LDV/SOF, respectively.
measure: Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Memory T Score
time frame: Baseline; Posttreatment Week 24
description: Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS).
For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.
measure: Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Attention Scaled Score
time frame: Baseline; Posttreatment Week 24
description: Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS).
For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.
measure: Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
time frame: Baseline; Posttreatment Week 24
description: Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS).
For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.
measure: Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
time frame: Baseline; Posttreatment Week 24
description: Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age & education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4).
For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.
measure: Change From Baseline in Neurocognitive Function at 24 Weeks After Discontinuation of Therapy: Motor
time frame: Baseline; Posttreatment Week 24
description: Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot).
For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.
measure: Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Short Form 36 (SF-36) Health Survey Scale - Physical Component Score
time frame: Baseline; Posttreatment Weeks 4 and 24
description: The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The first 6 concepts constitute the physical component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower scores representing more disability and higher scores representing less disability.
measure: Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by SF-36 Health Survey Scale - Mental Component Score
time frame: Baseline; Posttreatment (PT) Weeks 4 and 24
description: The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The last 5 concepts constitute the mental component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower score representing more disability and higher scores representing less disability.
measure: Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Chronic Liver Disease Questionnaire - HCV (CLDQ-HCV)
time frame: Baseline; Posttreatment Weeks 4 and 24
description: The CLDQ-HCV is a disease-specific questionnaire measuring health-related quality of life. CLDQ-HCV scores are calculated using participant responses to 29 questions divided into 4 domains: Activity/Energy, Emotion, Worry, and Systemic. An overall CLDQ-HCV score is calculated by taking the mean of all domain scores. Overall CLDQ-HCV scores range between 1 and 7, with higher scores representing better quality of life.
measure: Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
time frame: Baseline; Posttreatment Weeks 4 and 24
description: The FACIT-Fatigue score was measured using a 40-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale from 0 (Not at all) to 4 (Very much). The FACIT-F total score was calculated by taking the sum of all 40 individual scores and ranged from 0-160, with higher scores indicating better quality of life.
measure: Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Work Productivity and Activity Impairment Questionnaire, Hepatitis C (WPAI: Hepatitis C) - Overall Work Impairment
time frame: Baseline; Posttreatment Weeks 4 and 24
description: Impairment in overall work productivity was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall work impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from working).
measure: Change From Baseline in Health-Related Quality of Life at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by WPAI: Hepatitis C - Activity Impairment
time frame: Baseline; Posttreatment Weeks 4 and 24
description: Activity impairment was measured using the WPAI: Hepatitis C questionnaire completed by participants during study visits throughout the study. This questionnaire measured the effect of hepatitis C on the ability to work and perform regular activities. Overall activity impairment is expressed as a percentage and ranges from 0% (no effect) to 100% (completely prevented from performing regular activities).
measure: Change From Pre-treatment Assessment in Mood Related Assessment at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Beck Depression Inventory-II (BDI-II)
time frame: Baseline; Posttreatment Weeks 4 and 24
description: The BDI-II is a 21-item self-report instrument for measuring the severity of depression. Each item is rated on a 4-point scale ranging from 0 to 3. The item scores are summed to yield a derived total score that can range from 0 to 63 with lower values indicating less depression.
measure: Change From Pre-treatment Assessment in Mood Related Assessment at 4 and 24 Weeks After Discontinuation of Therapy as Assessed by Beck Hopelessness Scale (BHS)
time frame: Baseline; Posttreatment Weeks 4 and 24
description: The BHS is a 20-item scale for measuring the extent of negative attitudes about the future (pessimism) as perceived by adolescents and adults. The BHS consists of 20 true-false statements. Each of the 20 statements is scored 1 or 0. Of the 20 true-false statements, 9 are keyed FALSE, and 11 are keyed TRUE to indicate endorsement of pessimism about the future. The item scores are summed to yield a total score that can range from 0 to 20 with higher scores indicating greater hopelessness.
arm group label: LDV/SOF
arm group type: Experimental
description: Participants will receive LDV/SOF FDC for 12 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive LDV/SOF placebo for 12 weeks.
arm group label: Open-Label Treatment Phase
arm group type: Experimental
description: Following Posttreatment Week 4, participants in the placebo group will be offered open-label treatment with LDV/SOF FDC for 12 weeks.
intervention type: Drug
intervention name: LDV/SOF
description: 90/400 mg FDC tablet administered orally once daily
arm group label: LDV/SOF
arm group label: Open-Label Treatment Phase
other name: Harvoni®
other name: GS-5885/GS-7977
intervention type: Drug
intervention name: Placebo
description: Tablet administered orally once daily
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Benedetta Massetto, MD
role: Study Director
affiliation: Gilead Sciences
facility: 
country: United States
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Hepatitis C
mesh term: Sofosbuvir
mesh term: Ledipasvir, sofosbuvir drug combination
mesh term: Ledipasvir
sharing ipd: Yes
ipd description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: 18 months after study completion
ipd access criteria: A secured external environment with username, password, and RSA code.
ipd url: http://www.gilead.com/research/disclosure-and-transparency
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 