A Study of MK-0616 (Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids

Study Overview
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Brief Summary
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The goal of this study is to evaluate the efficacy, safety, and tolerability of MK-0616 in adult participants with hypercholesterolemia. The primary hypothesis is that MK-0616 is superior to placebo on mean percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 24.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-0616 in Adults With Hypercholesterolemia

Conditions
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Hypercholesterolemia, Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: MK-0616
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a history of a major atherosclerotic cardiovascular disease (ASCVD) event and LDL-C ≥55 mg/dL OR, if no history of a major ASCVD event, has intermediate to high risk for development of a first major ASCVD event and LDL-C ≥70 mg/dL. Is treated with a moderate- or high-intensity statin OR is treated with low-intensity statin with documentation of intolerance to a moderate or high-intensity statin OR is not receiving statins with documentation of statin intolerance If on any lipid-lowering therapies (LLTs), should be on a stable dose with no planned medication change. Exclusion Criteria: Has a history of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria, compound heterozygous FH, or double heterozygous FH Has a history of heart failure or heart failure hospitalization within 3 months before first study visit Is undergoing or previously underwent an LDL-C apheresis program within 3 months before first study visit or plans to initiate an LDL-C apheresis program Was previously treated/is being treated with certain other cholesterol lowering medications, including protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors without adequate washout

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-0616<br>Participants will receive 20 mg of MK-0616 orally once daily (QD) for up to 52 weeks. | Drug: MK-0616<br>* Oral tablet<br>|
| Placebo Comparator: Placebo<br>Participants will receive MK-0616-matching placebo orally QD for up to 52 weeks. | Drug: Placebo<br>* Oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 24 | Blood samples will be collected at baseline and at Week 24 to assess mean percent change in LDL-C. | Baseline and Week 24 | 
| Number of participants with one or more adverse events (AEs) | 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. | Up to  60 weeks | 
| Number of participants who discontinue study drug due to an AE | 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. | Up to  52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean percent change from baseline in LDL-C at Week 52 | Blood samples will be collected at baseline and at Week 52 to assess mean percent change in LDL-C. | Baseline and Week 52 | 
| Mean percent change from baseline in non-high-density lipoprotein cholesterol (non-HDL-C) at Week 24 | Blood samples will be collected at baseline and at Week 24 to assess mean percent change in non-HDL-C. | Baseline and Week 24 | 
| Mean percent change from baseline in apolipoprotein B (ApoB) at Week 24 | Blood samples will be collected at baseline and at Week 24 to assess mean percent change in ApoB. | Baseline and Week 24 | 
| Percent change from baseline in lipoprotein(a) (Lp[a]) at Week 24 | Blood samples will be collected at baseline and at Week 24 to assess percent change in Lp(a). | Baseline and Week 24 | 
| Percentage of participants with LDL-C <70 mg/dL and ≥50% reduction from baseline at Week 24 | Blood samples will be collected at baseline and at Week 24 to assess the percentage of participants who have LDL-C <70 mg/dL and ≥50% reduction from baseline. | Baseline and Week 24 | 
| Percentage of participants with LDL-C <55 mg/dL and ≥50% reduction from baseline at Week 24 | Blood samples will be collected at baseline and at Week 24 to assess the percentage of participants who have LDL-C <55 mg/dL and ≥50% reduction from baseline. | Baseline and Week 24 |