<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/NCT03782662</url>
  </required_header>
  <id_info>
    <org_study_id>REVC004</org_study_id>
    <secondary_id>2018-003256-21</secondary_id>
    <nct_id>NCT03782662</nct_id>
  </id_info>
  <brief_title>Drug Interaction Study With RV521 in Healthy Volunteer Subjects</brief_title>
  <official_title>An Adaptive, Part Open-label, Part Randomised Phase 1 Clinical Trial in Healthy Volunteers to Study Drug Interactions With RV521 Including Those Mediated by CYP3A4 and P-glycoprotein</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main aim of this study is to determine whether RV521 interacts with any other medication&#xD;
      using four licensed medicines (midazolam, itraconazole, rifampicin and verapamil) that are&#xD;
      known to have specific effects on enzymes and transporter proteins that influence the&#xD;
      absorption of drugs&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 6, 2018</start_date>
  <completion_date type="Actual">March 17, 2019</completion_date>
  <primary_completion_date type="Actual">March 17, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effect of RV521 on Cmax of Midazolam</measure>
    <time_frame>Baseline to study day 17</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of RV521 on tmax of Midazolam</measure>
    <time_frame>Baseline to study day 17</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of RV521 on t1/2 of Midazolam</measure>
    <time_frame>Baseline to study day 17</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of RV521 on AUC of Midazolam</measure>
    <time_frame>Baseline to study day 17</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of RV521 on CL/F of Midazolam</measure>
    <time_frame>Baseline to study day 17</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of itraconazole on Cmax of RV521</measure>
    <time_frame>Baseline to study day 12</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of itraconazole on tmax of RV521</measure>
    <time_frame>Baseline to study day 12</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of itraconazole on t1/2 of RV521</measure>
    <time_frame>Baseline to study day 12</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of itraconazole on AUC of RV521</measure>
    <time_frame>Baseline to study day 12</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of itraconazole on CL/F of RV521</measure>
    <time_frame>Baseline to study day 12</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of verapamil on Cmax of RV521</measure>
    <time_frame>Baseline to study day 16</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of verapamil on tmax of RV521</measure>
    <time_frame>Baseline to study day 16</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of verapamil on t1/2 of RV521</measure>
    <time_frame>Baseline to study day 16</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of verapamil on AUC of RV521</measure>
    <time_frame>Baseline to study day 16</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of verapamil on CL/F of RV521</measure>
    <time_frame>Baseline to study day 16</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of rifampicin on Cmax of RV521</measure>
    <time_frame>Baseline to study day 15</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of rifampicin on tmax of RV521</measure>
    <time_frame>Baseline to study day 15</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of rifampicin on t1/2 of RV521</measure>
    <time_frame>Baseline to study day 15</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of rifampicin on AUC of RV521</measure>
    <time_frame>Baseline to study day 15</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of rifampicin on CL/F of RV521</measure>
    <time_frame>Baseline to study day 15</time_frame>
    <description>The specified pharmacokinetic parameter will be summarised using descriptive statistics</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with treatment-related adverse events as assessed by NCI CTCAE V5.0</measure>
    <time_frame>Screening to final study visit (performed at 7 days following the last dose of any intervention)</time_frame>
    <description>The number of subjects with treatment-related adverse events will be summarised by treatment group using descriptive statistics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with QT/QTc interval changes relative to baseline who received RV521 (monotherapy), Midazolam (monotherapy) or RV521 and Midazolam (combination therapy)</measure>
    <time_frame>Baseline to to final study visit (performed at 7 days following the last dose of any intervention)</time_frame>
    <description>Descriptive statistics will be given by time point and dose-group for absolute values and change from baseline. Results will be tabulated and for QTc, the difference to time matched placebo will also be displayed</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">82</enrollment>
  <condition>Respiratory Syncytial Virus Infections</condition>
  <arm_group>
    <arm_group_label>RV521 plus Itraconazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D7 plus Itraconazole 100 mg capsules for oral administration, a 200 mg dose administered once daily on D4 - D10, inclusive</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RV521 plus Verapamil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D11 plus Verapamil, 80 mg tablets for oral administration, an 80 mg dose administered TDS daily on D4 - D14, inclusive</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RV521 plus Rifampicin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D10 plus Rifadin, Rifampicin, 300 mg capsules for oral administration, a 600 mg dose administered once daily on D4 - D10, inclusive</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RV521 plus Midazolam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RV521 drug substance in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo plus Midazolam</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo for RV521 in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Itraconazole</intervention_name>
    <description>Itraconazole capsules</description>
    <arm_group_label>RV521 plus Itraconazole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Verapamil</intervention_name>
    <description>Verapamil tablets</description>
    <arm_group_label>RV521 plus Verapamil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rifampicin</intervention_name>
    <description>Rifampicin capsules</description>
    <arm_group_label>RV521 plus Rifampicin</arm_group_label>
    <other_name>Rifadin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <description>Midazolam oromucosal solution</description>
    <arm_group_label>Placebo plus Midazolam</arm_group_label>
    <arm_group_label>RV521 plus Midazolam</arm_group_label>
    <other_name>Midazolam Prefilled Syringe</other_name>
    <other_name>Buccolam</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for RV521</intervention_name>
    <description>Placebo for RV521 capsules</description>
    <arm_group_label>Placebo plus Midazolam</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RV521</intervention_name>
    <description>RV521 capsules</description>
    <arm_group_label>RV521 plus Itraconazole</arm_group_label>
    <arm_group_label>RV521 plus Midazolam</arm_group_label>
    <arm_group_label>RV521 plus Rifampicin</arm_group_label>
    <arm_group_label>RV521 plus Verapamil</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 to 45 years, inclusive&#xD;
&#xD;
          -  Willing to comply with protocol defined contraception requirements&#xD;
&#xD;
          -  In good health with no history of major medical conditions&#xD;
&#xD;
          -  A body mass index (BMI) of 18 - 25 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of any clinically significant or currently active major medical condition&#xD;
&#xD;
          -  Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab),&#xD;
             or human immunodeficiency virus antibody (HIV Ab)&#xD;
&#xD;
          -  Not willing to comply with protocol defined restrictions for intake of drugs of abuse,&#xD;
             alcohol, nicotine-containing products, medication (prescription, OTC, herbal,&#xD;
             vitamins/minerals etc) and specified food and drink products&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lorch, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Richmond Pharmacology Limited</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Richmond Pharmacology Ltd</name>
      <address>
        <city>London</city>
        <zip>SE1 1YR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>December 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>May 22, 2019</last_update_submitted>
  <last_update_submitted_qc>May 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2019</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>Respiratory Syncytial Virus Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Itraconazole</mesh_term>
    <mesh_term>Rifampin</mesh_term>
    <mesh_term>Verapamil</mesh_term>
    <mesh_term>Midazolam</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03782662
org study id: REVC004
secondary id: 2018-003256-21
nct id: NCT03782662
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The main aim of this study is to determine whether RV521 interacts with any other medication
      using four licensed medicines (midazolam, itraconazole, rifampicin and verapamil) that are
      known to have specific effects on enzymes and transporter proteins that influence the
      absorption of drugs
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Effect of RV521 on Cmax of Midazolam
time frame: Baseline to study day 17
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of RV521 on tmax of Midazolam
time frame: Baseline to study day 17
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of RV521 on t1/2 of Midazolam
time frame: Baseline to study day 17
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of RV521 on AUC of Midazolam
time frame: Baseline to study day 17
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of RV521 on CL/F of Midazolam
time frame: Baseline to study day 17
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of itraconazole on Cmax of RV521
time frame: Baseline to study day 12
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of itraconazole on tmax of RV521
time frame: Baseline to study day 12
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of itraconazole on t1/2 of RV521
time frame: Baseline to study day 12
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of itraconazole on AUC of RV521
time frame: Baseline to study day 12
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of itraconazole on CL/F of RV521
time frame: Baseline to study day 12
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of verapamil on Cmax of RV521
time frame: Baseline to study day 16
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of verapamil on tmax of RV521
time frame: Baseline to study day 16
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of verapamil on t1/2 of RV521
time frame: Baseline to study day 16
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of verapamil on AUC of RV521
time frame: Baseline to study day 16
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of verapamil on CL/F of RV521
time frame: Baseline to study day 16
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of rifampicin on Cmax of RV521
time frame: Baseline to study day 15
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of rifampicin on tmax of RV521
time frame: Baseline to study day 15
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of rifampicin on t1/2 of RV521
time frame: Baseline to study day 15
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of rifampicin on AUC of RV521
time frame: Baseline to study day 15
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Effect of rifampicin on CL/F of RV521
time frame: Baseline to study day 15
description: The specified pharmacokinetic parameter will be summarised using descriptive statistics
measure: Number of subjects with treatment-related adverse events as assessed by NCI CTCAE V5.0
time frame: Screening to final study visit (performed at 7 days following the last dose of any intervention)
description: The number of subjects with treatment-related adverse events will be summarised by treatment group using descriptive statistics
measure: Number of subjects with QT/QTc interval changes relative to baseline who received RV521 (monotherapy), Midazolam (monotherapy) or RV521 and Midazolam (combination therapy)
time frame: Baseline to to final study visit (performed at 7 days following the last dose of any intervention)
description: Descriptive statistics will be given by time point and dose-group for absolute values and change from baseline. Results will be tabulated and for QTc, the difference to time matched placebo will also be displayed
arm group label: RV521 plus Itraconazole
arm group type: Experimental
description: RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D7 plus Itraconazole 100 mg capsules for oral administration, a 200 mg dose administered once daily on D4 - D10, inclusive
arm group label: RV521 plus Verapamil
arm group type: Experimental
description: RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D11 plus Verapamil, 80 mg tablets for oral administration, an 80 mg dose administered TDS daily on D4 - D14, inclusive
arm group label: RV521 plus Rifampicin
arm group type: Experimental
description: RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D10 plus Rifadin, Rifampicin, 300 mg capsules for oral administration, a 600 mg dose administered once daily on D4 - D10, inclusive
arm group label: RV521 plus Midazolam
arm group type: Experimental
description: RV521 drug substance in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15
arm group label: Placebo plus Midazolam
arm group type: Placebo Comparator
description: Placebo for RV521 in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15
intervention type: Drug
intervention name: Itraconazole
description: Itraconazole capsules
arm group label: RV521 plus Itraconazole
intervention type: Drug
intervention name: Verapamil
description: Verapamil tablets
arm group label: RV521 plus Verapamil
intervention type: Drug
intervention name: Rifampicin
description: Rifampicin capsules
arm group label: RV521 plus Rifampicin
other name: Rifadin
intervention type: Drug
intervention name: Midazolam
description: Midazolam oromucosal solution
arm group label: Placebo plus Midazolam
arm group label: RV521 plus Midazolam
other name: Midazolam Prefilled Syringe
other name: Buccolam
intervention type: Drug
intervention name: Placebo for RV521
description: Placebo for RV521 capsules
arm group label: Placebo plus Midazolam
intervention type: Drug
intervention name: RV521
description: RV521 capsules
arm group label: RV521 plus Itraconazole
arm group label: RV521 plus Midazolam
arm group label: RV521 plus Rifampicin
arm group label: RV521 plus Verapamil
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Lorch, MD
role: Principal Investigator
affiliation: Richmond Pharmacology Limited
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Respiratory Syncytial Virus Infections
mesh term: Itraconazole
mesh term: Rifampin
mesh term: Verapamil
mesh term: Midazolam