MK-0616 Cardiovascular Outcomes Study

Phase 3

• Conditions: E780 Pure hypercholesterolaemia; Pure hypercholesterolaemia; E780

• Registration Number: PER-031-23
• Lead Sponsor: Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-14
• Last Update Posted: 20 August 2024

Recruitment & Eligibility

• Status: Without startig enrollment
• Sex: All
• Target Recruitment: 0

Inclusion Criteria

Type of Participant and Disease Characteristics: Is on a stable dose of all background LLTs (including statin and nonstatin agents) for at least 30 days before Visit 1 (Screening) with no medication or dose changes planned during the participation in the study.

Demographics: Is an individual of any sex/gender, who meets the age criteria as defined in Inclusion #1 [Type of Participant and Disease Characteristics: Meets the criteria for at least 1 of the following ASCVD event risk categories (A or B) ] at the time of providing informed consent.

Female Participants: A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a POCBP.
OR
• Is a POCBP.

Informed Consent: The participant (or legally acceptable representative) has provided documented informed consent/assent for the study. The participant may also provide consent/assent for FBR. However, the participant may participate in the study without participating in FBR.
Note: Refer to Appendix 7 for country-specific requirements.

Type of Participant and Disease Characteristics: Meets the criteria for at least 1 of the following ASCVD event risk categories (A or B):

A. History of Major ASCVD Event:
Age =18 years with a history of a major ASCVD event defined as at least 1 of the following (i-iii):
i. =30 days post MI (presumed Type 1 due to plaque rupture or erosion).
ii. =30 days post ischemic stroke (presumed due to atherosclerosis).
iii. =30 days post successful peripheral (carotid or lower extremity) arterial revascularization (surgical or endovascular) or major (ankle or above) amputation due to atherosclerosis.
OR
B. High Risk for First Major ASCVD Event and Not Meeting Criteria for A:
High risk for first major ASCVD event defined as at least 1 of the following (i-v):
i. Age =50 years with evidence of CAD:
• History of multivessel disease (=2 vessels with =50% stenosis), with or without revascularization, or
• Significant unrevascularized single-vessel disease (=50% stenosis of the left main coronary artery or =70% stenosis of any other single coronary artery), or
• CT coronary artery calcification score =300 Agatston units in a participant without a coronary revascularization prior to randomization.

ii. Age =50 years with evidence of atherosclerotic cerebrovascular disease:
• Prior TIA with =50% ipsilateral carotid stenosis, or
• Carotid artery stenosis of =70% in at least 1 artery or =50% in both arteries.

iii. Age =50 years with evidence of PAD:
• =50% stenosis in an infra-inguinal leg artery (eg, femoral, superficial femoral, popliteal, tibial) due to atherosclerosis, or
• Symptoms of claudication attributed to vascular disease with an ankle brach

Exclusion Criteria

Non-cardiac medical conditions: Has a history of nephrotic syndrome.

Non-cardiac medical conditions: Has history of severe renal insufficiency defined as eGFR <30 mL/min/1.73 m2 at Visit 1 (Screening) or has ESRD on dialysis. eGFR will be calculated according to Appendix 2.
Note: Refer to Appendix 7 for country-specific requirements.

Other Exclusions: Has a recent history of drug abuse (within the last year) or is a current user of illicit drugs at the time of Visit 1 (Screening).

Cardiovascular medical conditions: Has a history of homozygous FH based on genetic or clinical criteria, compound heterozygous FH, or double heterozygous FH.

Cardiovascular medical conditions: Has New York Heart Association Class IV heart failure, last known Left Ventricular Ejection Fraction =25% by any imaging method, or had a Heart Failure hospitalization within 3 months before Visit 1 (Screening).

Cardiovascular medical conditions: Has recurrent ventricular tachycardia within 3 months prior to randomization.

Cardiovascular medical conditions: Has QTc =500 ms (in the absence of intraventricular conduction delay and/or bundle branch block) based on an ECG performed within 6 months before or at Visit 1 (Screening).

Cardiovascular medical conditions: Has uncontrolled hypertension defined as sitting SBP >160 mm Hg or DBP >100 mm Hg at Visit 2 (Randomization) despite stable antihypertensive treatment.

Other Exclusions: Has a medical disorder, condition, or history thereof that in the opinion of the investigator would impair the participant’s ability to participate in or complete the study.

Cardiovascular medical conditions: Has a planned arterial revascularization procedure.

Non-cardiac medical conditions: Has any clinically significant malabsorption condition based on principal investigator’s assessment (eg, recurrent vomiting, inflammatory bowel disease with ongoing symptoms, chronic intestinal disease accompanied by a disturbance in digestion absorption, or a history of extensive resection of the upper GI tract).

Non-cardiac medical conditions: Has laboratory or clinical evidence of clinically significant hepatic conditions, including 1 or more of the following:
• ALT or AST =3x ULN at Visit 1 (Screening).
• Direct bilirubin >2x ULN at Visit 1 (Screeni

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Time will be calculated in terms of days since randomization.<br> NAME OF THE RESULT: EFFICACY: Time to first serious adverse cardiovascular event (MACE) extended based on CHD death.<br><br>Defined as any of the following events: death from coronary heart disease, MI, ischemic stroke (fatal and nonfatal), acute limb ischemia or major amputation, or urgent arterial revascularization (coronary, cerebrovascular, or peripheral).<br> PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE<br> PRIMARY RESULT: From randomization until the appearance of the possible events of the Endpoint or until the last follow-up in which the endpoints are evaluated (last information available).