<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/NCT04459767</url>
  </required_header>
  <id_info>
    <org_study_id>C4491006</org_study_id>
    <nct_id>NCT04459767</nct_id>
  </id_info>
  <brief_title>Investigation Of Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Single Doses Of Vupanorsen In Japanese Healthy Adult Participants With Elevated Triglycerides</brief_title>
  <official_title>A PHASE 1, RANDOMIZED, DOUBLE-BLIND, THIRD-PARTY OPEN, PLACEBO-CONTROLLED, SINGLE ASCENDING DOSE STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF-07285557 (VUPANORSEN) ADMINISTERED SUBCUTANEOUSLY IN JAPANESE HEALTHY ADULTS WITH ELEVATED TRIGLYCERIDES</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>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1, randomized, double blind, third party open (i.e., participant blind,&#xD;
      investigator blind and sponsor open), placebo controlled, single ascending dose study to&#xD;
      investigate the safety, tolerability, pharmacokinetic and pharmacodynamics of vupanorsen in&#xD;
      Japanese healthy adult participants with elevated triglycerides.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 6, 2020</start_date>
  <completion_date type="Actual">December 15, 2020</completion_date>
  <primary_completion_date type="Actual">December 15, 2020</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>Sequential Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of treatment related adverse events</measure>
    <time_frame>Day 0-90</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and clinically relevant changes in electrocardiogram</measure>
    <time_frame>Day 0-90</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and magnitude of abnormal laboratory findings</measure>
    <time_frame>Day 0-90</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and clinically relevant changes in pulse rate</measure>
    <time_frame>Day 0-90</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and clinically relevant changes in supine blood pressure</measure>
    <time_frame>Day 0-90</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma concentration (Cmax)</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach maximum observed plasma concentration (Tmax)</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time profile from time zero to 24 hours post-dose (AUC24h)</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time profile from time zero to 48 hours post-dose (AUC48h)</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time profile from time zero to the last measurable concentration (AUClast)</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time profile from time zero to infinity (AUCinf)</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half life (t1/2)</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution (Vz/F)</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent clearance (CL/F)</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage changes from baseline in serum angiopoietin-like protein 3</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage changes from baseline in total cholesterol</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage changes from baseline in low density lipoprotein cholesterol</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage changes from baseline in non-high-density lipoprotein cholesterol</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage changes from baseline in very low density lipoprotein cholesterol</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage changes from baseline in triglyceride</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage changes from baseline in apolipoprotein A-1</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage changes from baseline in apolipoprotein B total</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage changes from baseline in apolipoprotein C-III</measure>
    <time_frame>Day 0-90</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Vupanorsen 80 milligram (mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive one, 0.8 milliliter (mL) subcutaneous injection with vupanorsen 100 mg/mL solution</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vupanorsen 160 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive two, 0.8 mL subcutaneous injections with vupanorsen 100 mg/mL solution</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants in Cohort 1 (vupanorsen 80 mg) will receive one 0.8 mL subcutaneous injection with 0.9% sodium chloride in water.&#xD;
Participants in Cohort 2 (vupanorsen 160 mg) will receive two 0.8 mL subcutaneous injections with 0.9% sodium chloride in water.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vupanorsen</intervention_name>
    <description>80 mg subcutaneous injection</description>
    <arm_group_label>Vupanorsen 160 mg</arm_group_label>
    <arm_group_label>Vupanorsen 80 milligram (mg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subcutaneous injection</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female participants must be 20 to 65 years of age, inclusive, at the time of&#xD;
             signing the ICD.&#xD;
&#xD;
          2. Participants must have four Japanese grandparents born in Japan.&#xD;
&#xD;
          3. Male and female participants who are overtly healthy as determined by medical&#xD;
             evaluation including medical history, physical examination, laboratory tests (except&#xD;
             for TG levels), and 12 lead ECG monitoring.&#xD;
&#xD;
          4. Fasting TG &gt;= 90 mg/dL at Screening&#xD;
&#xD;
          5. Participants who are willing and able to comply with all scheduled visits, treatment&#xD;
             plan, laboratory tests, lifestyle considerations, and other study procedures.&#xD;
&#xD;
          6. BMI of 17.5 to 35.0 kg/m2; and a total body weight &gt;50 kg (110 lb)&#xD;
&#xD;
          7. Capable of giving signed informed consent as described in Appendix 1, which includes&#xD;
             compliance with the requirements and restrictions listed in the ICD and in this&#xD;
             protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Evidence or history of clinically significant hematological, renal, endocrine,&#xD;
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or&#xD;
             allergic disease.&#xD;
&#xD;
          2. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV,&#xD;
             HBsAg, or HCVAb.&#xD;
&#xD;
          3. Other medical or psychiatric condition including recent (within the past year) or&#xD;
             active suicidal ideation/behavior or laboratory abnormality that may increase the risk&#xD;
             of study participation or, in the investigator's judgment, make the participant&#xD;
             inappropriate for the study.&#xD;
&#xD;
          4. History of allergic or anaphylactic reaction.&#xD;
&#xD;
          5. Use of prescription or nonprescription drugs and dietary and herbal supplements within&#xD;
             7 days or 5 half lives (whichever is longer) prior to the first dose of study&#xD;
             intervention.&#xD;
&#xD;
          6. Previous administration with an investigational drug within 4 months or 5 half lives&#xD;
             preceding the first dose of study intervention used in this study (whichever is&#xD;
             longer).&#xD;
&#xD;
          7. A positive urine drug test.&#xD;
&#xD;
          8. Screening supine BP &gt;=140 mm Hg (systolic) or &gt;=90 mm Hg (diastolic), following at&#xD;
             least 5 minutes of supine rest. If BP is &gt;=140 mm Hg (systolic) or &gt;=90 mm Hg&#xD;
             (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values&#xD;
             should be used to determine the participant's eligibility.&#xD;
&#xD;
          9. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may&#xD;
             affect participant safety or interpretation of study results.&#xD;
&#xD;
         10. Participants with ANY of the following abnormalities in clinical laboratory tests at&#xD;
             screening, as assessed by the study specific laboratory and confirmed by a single&#xD;
             repeat test, if deemed necessary:&#xD;
&#xD;
               -  AST or ALT level &gt;=1.25 × ULN;&#xD;
&#xD;
               -  Total bilirubin level &gt;=1.5 × ULN; participants with a history of Gilbert's&#xD;
                  syndrome may have direct bilirubin measured and would be eligible for this study&#xD;
                  provided the direct bilirubin level is=&lt;ULN.&#xD;
&#xD;
         11. History of alcohol abuse or binge drinking and/or any other illicit drug use or&#xD;
             dependence within 6 months of Screening.&#xD;
&#xD;
         12. Blood donation (excluding plasma donations and platelet donations) of approximately&#xD;
             400 mL within 3 months or &gt;=200 mL within a month prior to dosing. Additionally,&#xD;
             approximately &gt;=400 mL within 4 months for female participants.&#xD;
&#xD;
         13. History of sensitivity to heparin or heparin induced thrombocytopenia.&#xD;
&#xD;
         14. History of substance abuse within 12 months of the screening visit.&#xD;
&#xD;
         15. Pregnant females; breastfeeding females.&#xD;
&#xD;
         16. Unwilling or unable to comply with the criteria in the Lifestyle Considerations&#xD;
             section of this protocol.&#xD;
&#xD;
         17. Investigator site staff or Pfizer employees directly involved in the conduct of the&#xD;
             study, site staff otherwise supervised by the investigator, and their respective&#xD;
             family members.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>P-one Clinic</name>
      <address>
        <city>Hachioji-shi</city>
        <state>Tokyo</state>
        <zip>192-0071</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <link>
    <url>https://pmiform.com/clinical-trial-info-request?StudyID=C4491006</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>December 18, 2020</last_update_submitted>
  <last_update_submitted_qc>December 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Triglycerides</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertriglyceridemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.</ipd_description>
  </patient_data>
  <!-- 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/NCT04459767
org study id: C4491006
nct id: NCT04459767
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a Phase 1, randomized, double blind, third party open (i.e., participant blind,
      investigator blind and sponsor open), placebo controlled, single ascending dose study to
      investigate the safety, tolerability, pharmacokinetic and pharmacodynamics of vupanorsen in
      Japanese healthy adult participants with elevated triglycerides.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Incidence of treatment related adverse events
time frame: Day 0-90
measure: Incidence of abnormal and clinically relevant changes in electrocardiogram
time frame: Day 0-90
measure: Incidence and magnitude of abnormal laboratory findings
time frame: Day 0-90
measure: Incidence of abnormal and clinically relevant changes in pulse rate
time frame: Day 0-90
measure: Incidence of abnormal and clinically relevant changes in supine blood pressure
time frame: Day 0-90
measure: Maximum observed plasma concentration (Cmax)
time frame: Day 0-90
measure: Time to reach maximum observed plasma concentration (Tmax)
time frame: Day 0-90
measure: Area under the plasma concentration-time profile from time zero to 24 hours post-dose (AUC24h)
time frame: Day 0-90
measure: Area under the plasma concentration-time profile from time zero to 48 hours post-dose (AUC48h)
time frame: Day 0-90
measure: Area under the plasma concentration-time profile from time zero to the last measurable concentration (AUClast)
time frame: Day 0-90
measure: Area under the plasma concentration-time profile from time zero to infinity (AUCinf)
time frame: Day 0-90
measure: Terminal elimination half life (t1/2)
time frame: Day 0-90
measure: Apparent volume of distribution (Vz/F)
time frame: Day 0-90
measure: Apparent clearance (CL/F)
time frame: Day 0-90
measure: Percentage changes from baseline in serum angiopoietin-like protein 3
time frame: Day 0-90
measure: Percentage changes from baseline in total cholesterol
time frame: Day 0-90
measure: Percentage changes from baseline in low density lipoprotein cholesterol
time frame: Day 0-90
measure: Percentage changes from baseline in non-high-density lipoprotein cholesterol
time frame: Day 0-90
measure: Percentage changes from baseline in very low density lipoprotein cholesterol
time frame: Day 0-90
measure: Percentage changes from baseline in triglyceride
time frame: Day 0-90
measure: Percentage changes from baseline in apolipoprotein A-1
time frame: Day 0-90
measure: Percentage changes from baseline in apolipoprotein B total
time frame: Day 0-90
measure: Percentage changes from baseline in apolipoprotein C-III
time frame: Day 0-90
arm group label: Vupanorsen 80 milligram (mg)
arm group type: Experimental
description: Participants will receive one, 0.8 milliliter (mL) subcutaneous injection with vupanorsen 100 mg/mL solution
arm group label: Vupanorsen 160 mg
arm group type: Experimental
description: Participants will receive two, 0.8 mL subcutaneous injections with vupanorsen 100 mg/mL solution
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants in Cohort 1 (vupanorsen 80 mg) will receive one 0.8 mL subcutaneous injection with 0.9% sodium chloride in water.
Participants in Cohort 2 (vupanorsen 160 mg) will receive two 0.8 mL subcutaneous injections with 0.9% sodium chloride in water.
intervention type: Drug
intervention name: Vupanorsen
description: 80 mg subcutaneous injection
arm group label: Vupanorsen 160 mg
arm group label: Vupanorsen 80 milligram (mg)
intervention type: Drug
intervention name: Placebo
description: Subcutaneous injection
arm group label: Placebo
criteria: 
gender: All
minimum age: 20 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
country: Japan
url: https://pmiform.com/clinical-trial-info-request?StudyID=C4491006
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Hypertriglyceridemia
sharing ipd: No
ipd description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.