A Study of the Efficacy and Safety of MK-0616 (Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-008)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of MK-0616, an oral PCSK9 inhibitor, in lowering low-density lipoprotein cholesterol (LDL-C) in participants with hypercholesterolemia. The primary hypothesis is that at least one of the four doses of MK-0616 tested in this study is superior to placebo on percent change from baseline in LDL-C at Week 8.

Official Title
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A Phase 2b, 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: History of clinical atherosclerotic cardiovascular disease (ASCVD), or has an ASCVD risk equivalent and/or a 10-year risk of having an ASCVD event ≥5.0%, AND has a corresponding LDL-C that falls within the protocol-specified range at screening. Treatment with a stable dose of one or more lipid-lowering therapies for ≥30 days before screening, or has not received treatment with any lipid-lowering therapy for ≥30 days before screening. A female participant is not pregnant or breastfeeding, not a woman of child-bearing potential (WOCBP) or is a WOCBP and agrees to follow contraceptive guidance during the intervention period and for at least 8 weeks after the last dose of study intervention. Exclusion Criteria: History of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria. History of nephrotic syndrome. History of unstable angina, a myocardial infarction, percutaneous transluminal coronary angioplasty, transient ischemic attack, or stroke within 3 months before Screening. Has poorly controlled diabetes mellitus, defined as hemoglobin A1C (A1C) ≥9.0% at Screening. History of malignancy ≤3 years before screening, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, which have no timeframe limitations relative to screening. Currently participating in or has previously participated in an interventional clinical study within 3 months before Screening. Has moderate or greater renal insufficiency.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-0616 6 mg<br>Participants will receive 6 mg of MK-0616 orally QD for 8 weeks | Drug: MK-0616<br>* MK-0616 administered orally<br>|
| Experimental: MK-0616 12 mg<br>Participants will receive 12 mg of MK-0616 orally QD for 8 weeks | Drug: MK-0616<br>* MK-0616 administered orally<br>|
| Experimental: MK-0616 18 mg<br>Participants will receive 18 mg of MK-0616 orally QD for 8 weeks | Drug: MK-0616<br>* MK-0616 administered orally<br>|
| Experimental: MK-0616 30 mg<br>Participants will receive 30 mg of MK-0616 orally QD for 8 weeks | Drug: MK-0616<br>* MK-0616 administered orally<br>|
| Placebo Comparator: Placebo<br>Participants will receive MK-0616-matching placebo orally QD for 8 weeks | Drug: Placebo<br>* Placebo matching MK-0616 administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 8 | Blood samples were collected at baseline and after 8 weeks of treatment to assess mean percent change in LDL-C. Based on a constrained longitudinal analysis (cLDA) model including terms for treatment, time, baseline statin intensity, baseline renal function, and the interaction of treatment by time. The percent change from baseline in LDL-C at week 8 was reported. | Baseline and up to Week 8 | 
| Percentage of Participants Who Experienced One or More Adverse Events (AEs) | An AE was 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. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced at least one AE was reported. | Up to approximately 17 Weeks | 
| Percentage of Participants Who Discontinued Study Intervention Due to AEs | An AE was 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. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study intervention due to AEs was reported. | Up to approximately 9 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 8 | Blood samples were collected at baseline and after 8 weeks of treatment to assess mean percent change in ApoB. The least square mean and 95% CI were obtained from fitting a cLDA model including terms for treatment, time, baseline statin intensity, baseline renal function, and the interaction of treatment by time. The percent change from baseline in ApoB at week 8 was reported. | Baseline and up to Week 8 | 
| Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 8 | Blood samples were collected at baseline and after 8 weeks of treatment to assess mean percent change in non-HDL-C. The least square mean and 95% CI were obtained from fitting a cLDA model including terms for treatment, time, baseline statin intensity, baseline renal function, and the interaction of treatment by time. The percent change from baseline in non-HDL-C at week 8 was reported. | Baseline and up to Week 8 | 
| Percentage of Participants With LDL-C Value at Goal at Week 8 | LDL-C goal was defined as: LDL-C <70 mg/dL (<1.81 mmol/L) in participants with clinical atherosclerotic cardiovascular disease (ASCVD), LDL-C <100 mg/dL (<2.59 mmol/L) in participants with an ASCVD risk-equivalent and/or a 10-year risk of having an ASCVD event that is ≥7.5%, OR LDL-C <130 mg/dL (<3.37mmol/L) in participants with a 10-year risk of having an ASCVD event that is ≥5.0% and <7.5%. The percentage of participants with LDL-C value at goal at week 8 were reported. | Week 8 |