xml: <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/NCT06008756</url>
    </required_header>
    <id_info>
      <org_study_id>0616-015</org_study_id>
      <nct_id>NCT06008756</nct_id>
    </id_info>
    <brief_title>MK-0616 (Oral PCSK9 Inhibitor) Cardiovascular Outcomes Study (MK-0616-015) CORALreef Outcomes</brief_title>
    <official_title>Phase 3 Randomized, Placebo-Controlled Clinical Study to Evaluate the Efficacy and Safety of MK-0616 in Reducing Major Adverse Cardiovascular Events in Participants at High Cardiovascular Risk</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Merck Sharp &amp; Dohme LLC</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Merck Sharp &amp; Dohme LLC</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a phase 3, randomized, placebo-controlled study of the efficacy and safety of&#xD;
        MK-0616, an oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in&#xD;
        participants with high cardiovascular risk. The primary objective is to evaluate the efficacy&#xD;
        of MK-0616 compared with placebo in increasing the time to the first occurrence of major&#xD;
        adverse cardiovascular events (MACE) including coronary heart disease (CHD) death, ischemic&#xD;
        stroke, myocardial infarction (MI), acute limb ischemia or major amputation, or urgent&#xD;
        arterial revascularization.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 25, 2023</start_date>
    <completion_date type="Anticipated">November 29, 2029</completion_date>
    <primary_completion_date type="Anticipated">November 29, 2029</primary_completion_date>
    <phase>Phase 3</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, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Time to First Occurrence of Coronary Heart Disease (CHD) Death-Based Major Adverse Cardiovascular Events (MACE)-Plus</measure>
      <time_frame>From date of randomization until the date of first occurrence of CHD death-based MACE-plus, assessed up to approximately 6 years</time_frame>
      <description>Time to the first occurrence of CHD death-based MACE-plus, which is defined as any of the following: coronary heart disease death, myocardial infarction (MI), ischemic stroke (fatal and nonfatal), acute limb ischemia or major amputation, or urgent arterial revascularization (coronary, cerebrovascular, or peripheral).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Time to First Occurrence of 3-point MACE</measure>
      <time_frame>From date of randomization until the date of first occurrence of 3-point MACE, assessed up to approximately 6 years</time_frame>
      <description>Time to the first occurrence of 3-point MACE (defined as cardiovascular death, MI, or ischemic stroke).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to First Occurrence of Cardiovascular (CV) Death-Based MACE Plus</measure>
      <time_frame>From date of randomization until the date of first occurrence of CV death-based MACE plus, assessed up to approximately 6 years</time_frame>
      <description>Time to the first occurrence of CV death-based MACE plus, defined as any of the following: cardiovascular death, MI, ischemic stroke, acute limb ischemia or major amputation, or urgent arterial revascularization (coronary, cerebrovascular, or peripheral).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to First Occurrence of CHD Death or MI</measure>
      <time_frame>From date of randomization until the date of first occurrence of CHD death or MI, assessed up to approximately 6 years</time_frame>
      <description>Time to the first occurrence of CHD death or MI.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to CV Death</measure>
      <time_frame>From date of randomization until the date of CV death, assessed up to approximately 6 years</time_frame>
      <description>Time to cardiovascular death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to All-Cause Death</measure>
      <time_frame>From date of randomization until the date of death, assessed up to approximately 6 years</time_frame>
      <description>Time to all-cause death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to CHD Death</measure>
      <time_frame>From date of randomization until the date of CHD death, assessed up to approximately 6 years</time_frame>
      <description>Time to CHD death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to First Event of MI</measure>
      <time_frame>From date of randomization until the date of MI, assessed up to approximately 6 years</time_frame>
      <description>Time to the first occurrence of MI.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to First Event of Ischemic Stroke</measure>
      <time_frame>From date of randomization until the date of first occurrence of ischemic stroke, assessed up to approximately 6 years</time_frame>
      <description>Time to the first occurrence of ischemic stroke.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to First Event of Acute Limb Ischemia or Major Amputation</measure>
      <time_frame>From date of randomization until the date of first occurrence of acute limb ischemia or major amputation, assessed up to approximately 6 years</time_frame>
      <description>Time to the first occurrence of acute limb ischemia or major amputation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to First Event of Urgent Arterial Revascularization</measure>
      <time_frame>From date of randomization until the date of urgent arterial revascularization, assessed up to approximately 6 years</time_frame>
      <description>Time to the first occurrence of urgent arterial revascularization (coronary, cerebrovascular, or peripheral).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percent Change from Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)</measure>
      <time_frame>Baseline and Week 52</time_frame>
      <description>The percent change from baseline in LDL-C.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percent Change from Baseline in Apolipoprotein B</measure>
      <time_frame>Baseline and Week 52</time_frame>
      <description>The percent change from baseline in apolipoprotein B.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percent Change from Baseline in Non-High-Density Lipoprotein Cholesterol (non-HDL-C) cholesterol</measure>
      <time_frame>Baseline and Week 52</time_frame>
      <description>The percent change from baseline in Non-HDL-C.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percent Change from Baseline in Lipoprotein (a)</measure>
      <time_frame>Baseline and Week 52</time_frame>
      <description>The percent change from baseline in lipoprotein (a).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with an Adverse Event (AE)</measure>
      <time_frame>Up to ~6 years</time_frame>
      <description>An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with AE(s) in each arm will be reported.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants Discontinuing from Study Therapy Due to AE</measure>
      <time_frame>Up to ~6 years</time_frame>
      <description>An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants discontinuing due to AE(s) in each arm will be reported.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">14550</enrollment>
    <condition>Arteriosclerosis</condition>
    <condition>Hypercholesterolaemia</condition>
    <arm_group>
      <arm_group_label>MK-0616</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants receive MK-0616 20 mg once daily.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Participants receive placebo once daily.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>MK-0616</intervention_name>
      <description>MK-0616 20 mg tablet taken by mouth.</description>
      <arm_group_label>MK-0616</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo tablet matched to MK-0616 taken by mouth.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Meets one of the following:&#xD;
  &#xD;
                 1. Age ≥18 years with a history of a major atherosclerotic cardiovascular disease&#xD;
                    (ASCVD) event defined as at least 1 of the following: ≥30 days post MI (presumed&#xD;
                    Type 1 due to plaque rupture or erosion); ≥30 days post ischemic stroke (presumed&#xD;
                    due to atherosclerosis); or ≥30 days post successful peripheral (carotid or lower&#xD;
                    extremity) arterial revascularization (surgical or endovascular) or major (ankle&#xD;
                    or above) amputation due to atherosclerosis; or&#xD;
  &#xD;
                 2. High risk for first major ASCVD event defined as at least 1 of the following: Age&#xD;
                    ≥50 years with evidence of coronary artery disease; Age ≥50 years with evidence&#xD;
                    of atherosclerotic cerebrovascular disease; Age ≥50 years with evidence of&#xD;
                    peripheral arterial disease; or Age ≥60 years with diabetes mellitus and at least&#xD;
                    one of the following: microvascular disease or urine albumin-creatinine ratio ≥30&#xD;
                    mg/mmol within 6 months before Visit 1, daily insulin use, or diabetes for ≥10&#xD;
                    years&#xD;
  &#xD;
            -  Has fasted lipid values (evaluated by the Central Laboratory) at Visit 1 (Screening)&#xD;
               as follows:&#xD;
  &#xD;
                 1. History of major ASCVD Event: LDL-C ≥70 mg/dL (1.81 mmol/L) OR non-HDL-C ≥100&#xD;
                    mg/dL (2.59 mmol/L)&#xD;
  &#xD;
                 2. High risk for first major ASCVD Event: LDL-C ≥90 mg/dL (2.33 mmol/L) OR non-HDL-C&#xD;
                    ≥120 mg/dL (3.11 mmol/L)&#xD;
  &#xD;
            -  Is treated with moderate- or high-intensity statin (± nonstatin lipid-lowering therapy&#xD;
               [LLT]) at Visit 1&#xD;
  &#xD;
            -  Is on a stable dose of all background LLTs (including statin and nonstatin agents) for&#xD;
               at least 30 days before Visit 1 (Screening) with no medication or dose changes planned&#xD;
               during the participation in the study&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Has a history of homozygous familial hypercholesterolemia (FH) based on genetic or&#xD;
               clinical criteria, compound heterozygous FH, or double heterozygous FH&#xD;
  &#xD;
            -  Has New York Heart Association Class IV heart failure, last known Left Ventricular&#xD;
               Ejection Fraction ≤25% by any imaging method, or had a Heart Failure hospitalization&#xD;
               within 3 months before Visit 1 (Screening)&#xD;
  &#xD;
            -  Has recurrent ventricular tachycardia within 3 months prior to randomization&#xD;
  &#xD;
            -  Has a planned arterial revascularization procedure&#xD;
  &#xD;
            -  Is undergoing or previously underwent an LDL-C apheresis program within 3 months&#xD;
               before Visit 1 (Screening) or plans to initiate an LDL-C apheresis program&#xD;
  &#xD;
            -  Was previously treated/is being treated with certain other cholesterol lowering&#xD;
               medications, including protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors&#xD;
               without adequate washout.&#xD;
  &#xD;
            -  Has a fasting triglyceride value ≥400 mg/dL (≥4.52 mmol/L) at Visit 1 (Screening)&#xD;
  &#xD;
            -  Has history of severe renal insufficiency defined as estimated glomerular filtration&#xD;
               rate &lt;30 mL/min/1.73 m2 at Visit 1 (Screening) or has end-stage renal disease on&#xD;
               dialysis.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <link>
      <url>http://www.merckclinicaltrials.com</url>
      <description>Merck Clinical Trials Information</description>
    </link>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</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>Arteriosclerosis</mesh_term>
      <mesh_term>Hypercholesterolemia</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
      <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06008756
  org study id: 0616-015
  nct id: NCT06008756
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a phase 3, randomized, placebo-controlled study of the efficacy and safety of
        MK-0616, an oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in
        participants with high cardiovascular risk. The primary objective is to evaluate the efficacy
        of MK-0616 compared with placebo in increasing the time to the first occurrence of major
        adverse cardiovascular events (MACE) including coronary heart disease (CHD) death, ischemic
        stroke, myocardial infarction (MI), acute limb ischemia or major amputation, or urgent
        arterial revascularization.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Time to First Occurrence of Coronary Heart Disease (CHD) Death-Based Major Adverse Cardiovascular Events (MACE)-Plus
  time frame: From date of randomization until the date of first occurrence of CHD death-based MACE-plus, assessed up to approximately 6 years
  description: Time to the first occurrence of CHD death-based MACE-plus, which is defined as any of the following: coronary heart disease death, myocardial infarction (MI), ischemic stroke (fatal and nonfatal), acute limb ischemia or major amputation, or urgent arterial revascularization (coronary, cerebrovascular, or peripheral).
  measure: Time to First Occurrence of 3-point MACE
  time frame: From date of randomization until the date of first occurrence of 3-point MACE, assessed up to approximately 6 years
  description: Time to the first occurrence of 3-point MACE (defined as cardiovascular death, MI, or ischemic stroke).
  measure: Time to First Occurrence of Cardiovascular (CV) Death-Based MACE Plus
  time frame: From date of randomization until the date of first occurrence of CV death-based MACE plus, assessed up to approximately 6 years
  description: Time to the first occurrence of CV death-based MACE plus, defined as any of the following: cardiovascular death, MI, ischemic stroke, acute limb ischemia or major amputation, or urgent arterial revascularization (coronary, cerebrovascular, or peripheral).
  measure: Time to First Occurrence of CHD Death or MI
  time frame: From date of randomization until the date of first occurrence of CHD death or MI, assessed up to approximately 6 years
  description: Time to the first occurrence of CHD death or MI.
  measure: Time to CV Death
  time frame: From date of randomization until the date of CV death, assessed up to approximately 6 years
  description: Time to cardiovascular death.
  measure: Time to All-Cause Death
  time frame: From date of randomization until the date of death, assessed up to approximately 6 years
  description: Time to all-cause death.
  measure: Time to CHD Death
  time frame: From date of randomization until the date of CHD death, assessed up to approximately 6 years
  description: Time to CHD death.
  measure: Time to First Event of MI
  time frame: From date of randomization until the date of MI, assessed up to approximately 6 years
  description: Time to the first occurrence of MI.
  measure: Time to First Event of Ischemic Stroke
  time frame: From date of randomization until the date of first occurrence of ischemic stroke, assessed up to approximately 6 years
  description: Time to the first occurrence of ischemic stroke.
  measure: Time to First Event of Acute Limb Ischemia or Major Amputation
  time frame: From date of randomization until the date of first occurrence of acute limb ischemia or major amputation, assessed up to approximately 6 years
  description: Time to the first occurrence of acute limb ischemia or major amputation.
  measure: Time to First Event of Urgent Arterial Revascularization
  time frame: From date of randomization until the date of urgent arterial revascularization, assessed up to approximately 6 years
  description: Time to the first occurrence of urgent arterial revascularization (coronary, cerebrovascular, or peripheral).
  measure: Percent Change from Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)
  time frame: Baseline and Week 52
  description: The percent change from baseline in LDL-C.
  measure: Percent Change from Baseline in Apolipoprotein B
  time frame: Baseline and Week 52
  description: The percent change from baseline in apolipoprotein B.
  measure: Percent Change from Baseline in Non-High-Density Lipoprotein Cholesterol (non-HDL-C) cholesterol
  time frame: Baseline and Week 52
  description: The percent change from baseline in Non-HDL-C.
  measure: Percent Change from Baseline in Lipoprotein (a)
  time frame: Baseline and Week 52
  description: The percent change from baseline in lipoprotein (a).
  measure: Number of Participants with an Adverse Event (AE)
  time frame: Up to ~6 years
  description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with AE(s) in each arm will be reported.
  measure: Number of Participants Discontinuing from Study Therapy Due to AE
  time frame: Up to ~6 years
  description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants discontinuing due to AE(s) in each arm will be reported.
  arm group label: MK-0616
  arm group type: Experimental
  description: Participants receive MK-0616 20 mg once daily.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Participants receive placebo once daily.
  intervention type: Drug
  intervention name: MK-0616
  description: MK-0616 20 mg tablet taken by mouth.
  arm group label: MK-0616
  intervention type: Drug
  intervention name: Placebo
  description: Placebo tablet matched to MK-0616 taken by mouth.
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  url: http://www.merckclinicaltrials.com
  description: Merck Clinical Trials Information
  responsible party type: Sponsor
  mesh term: Arteriosclerosis
  mesh term: Hypercholesterolemia
  sharing ipd: Yes
  ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
  ipd url: http://engagezone.msd.com/ds_documentation.php