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

The primary objective of this study is to evaluate the **efficacy** of MK-0616 compared with placebo on the mean percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 24. This is clinically relevant as LDL-C is a major risk factor for cardiovascular diseases, and effective management of LDL-C levels is crucial in patients with Heterozygous Familial Hypercholesterolemia (HeFH). Additionally, the study aims to assess the safety and tolerability of MK-0616.

Secondary objectives include: - Evaluating the efficacy of MK-0616 compared with placebo on mean percent change from baseline in LDL-C at Week 52. - Assessing the mean percent change from baseline in non-high-density lipoprotein cholesterol (non-HDL-C) at Week 24. - Evaluating the mean percent change from baseline in apolipoprotein B (ApoB) at Week 24. - Assessing the percent change from baseline in lipoprotein(a) [Lp(a)] at Week 24. - Evaluating the proportion of participants achieving LDL-C levels <70 mg/dL and ≥50% reduction from baseline at Week 24. - Assessing the proportion of participants achieving LDL-C levels <55 mg/dL and ≥50% reduction from baseline at Week 24.

The clinical trial involves a total of **235 participants** diagnosed with **Heterozygous Familial Hypercholesterolemia (HeFH)**. The study population includes both male and female subjects, with an age range that corresponds to categories 3 and 4, indicating a broad adult demographic. Participants were selected based on a locally accepted diagnostic algorithm for HeFH and are required to have an LDL-C level of at least 55 mg/dL or 70 mg/dL, contingent on their medical history. All participants are currently on a stable regimen of moderate- or high-intensity statin medication, with no planned changes to their lipid-lowering therapies. The trial includes individuals from a vulnerable population, ensuring a comprehensive evaluation of the treatment's efficacy and safety across diverse health profiles. Lifestyle factors such as diet and physical activity were not specified in the available data.

The clinical trial is a **Phase 3, randomized, double-blind, placebo-controlled** study designed to evaluate the efficacy and safety of MK-0616 in adults diagnosed with **heterozygous familial hypercholesterolemia** (HeFH). The primary objective is to assess the mean percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 24, alongside evaluating the safety and tolerability of MK-0616. The trial is expected to span approximately 52 weeks, with participant recruitment having commenced on September 1, 2023, and an estimated end date of April 28, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a definite diagnosis of HeFH, LDL-C levels, and stable lipid-lowering therapy. Following randomization, participants will receive either MK-0616 or a placebo, administered orally in the form of a film-coated tablet. The study includes regular follow-up visits to monitor efficacy and safety endpoints, with key assessments at Weeks 24 and 52. The end-of-study visit will conclude the trial, where final evaluations will be conducted.

Participant involvement is expected to last for the full duration of the trial, approximately one year, unless early termination is warranted. Conditions for early termination include the occurrence of adverse events (AEs) that necessitate discontinuation of the study drug. The primary endpoints include the mean percent change in LDL-C at Week 24 and the number of participants experiencing AEs or discontinuing due to AEs. Secondary endpoints will assess changes in other lipid parameters and the percentage of participants achieving specific LDL-C reduction targets.

The clinical trial involves the administration of **MK-0616**, an investigational medication, in the form of a film-coated tablet. The active substance in MK-0616 is **enlicitide chloride**, a chemical compound. The medication is administered orally with a maximum daily dose of 20 mg. The total maximum dose over the treatment period is 73,000 mg, with the treatment duration extending up to 52 weeks. The trial aims to evaluate the efficacy and safety of MK-0616 in adults with heterozygous familial hypercholesterolemia. Participant compliance with the dosing schedule will be monitored throughout the study.

In addition to the experimental treatment, a **placebo** is used as a comparator in this double-blind, placebo-controlled study. The placebo is designed to mimic the appearance of the MK-0616 tablet but does not contain the active substance. It is also administered orally in the same pharmaceutical form as the investigational drug. The use of a placebo allows for the assessment of the true efficacy and safety profile of MK-0616 by providing a baseline for comparison. Participants will be randomly assigned to receive either the investigational drug or the placebo, ensuring the study's integrity and reliability.

The efficacy of MK-0616 in the treatment of **heterozygous familial hypercholesterolemia** will be assessed through a Phase 3, randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the mean percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 24. Secondary endpoints include the mean percent change from baseline in LDL-C at Week 52, non-high-density lipoprotein cholesterol (HDL-C) at Week 24, and apolipoprotein B (ApoB) at Week 24. Additionally, the percent change from baseline in lipoprotein(a) (Lp[a]) at Week 24 and the percentage of participants achieving specific LDL-C targets at Week 24 will be measured.

Efficacy parameters will be collected and analyzed at specified timepoints, including Week 24 and Week 52, using validated laboratory tests to measure lipid levels. The trial will also monitor the percentage of participants achieving LDL-C levels below 70 mg/dL and 55 mg/dL with a reduction of at least 50% from baseline at Week 24. These assessments will provide comprehensive data on the efficacy of MK-0616 in reducing cholesterol levels in the target population.