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

The primary objective of this Phase 3, randomized, double-blind, placebo-controlled 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. Additionally, the study aims to assess the safety and tolerability of MK-0616. This is clinically relevant as reducing LDL-C is a critical factor in managing **hypercholesterolemia**, which is associated with an increased risk of cardiovascular diseases.

Secondary objectives include evaluating the efficacy of MK-0616 compared with placebo on:

• Mean percent change from baseline in LDL-C at Week 52.
• Mean percent change from baseline in non-high-density lipoprotein cholesterol (non-HDL-C) at Week 24.
• Mean percent change from baseline in apolipoprotein B (ApoB) at Week 24.
• Percent change from baseline in lipoprotein(a) [Lp(a)] at Week 24.
• The proportion of participants achieving LDL-C levels of less than 70 mg/dL and a reduction of 50% or more from baseline at Week 24.
• The proportion of participants achieving LDL-C levels of less than 55 mg/dL and a reduction of 50% or more from baseline at Week 24.

The clinical trial involves a total of **2360 participants** diagnosed with **hypercholesterolemia**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific criteria, including a history of major atherosclerotic cardiovascular disease (ASCVD) events or an intermediate to high risk for such events. The trial includes individuals with varying levels of LDL-C, depending on their ASCVD history, and considers their current treatment with statins or other lipid-lowering therapies. Participants are required to be on a stable dose of any lipid-lowering treatments for at least 30 days prior to screening, with no planned changes during the study. The trial also includes a vulnerable population, ensuring a comprehensive evaluation of the efficacy and safety of the investigational drug MK-0616 compared to placebo. Lifestyle factors such as diet and physical activity are 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 with **hypercholesterolemia**. The trial aims 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 study will involve the administration of MK-0616, a film-coated tablet containing **enlicitide chloride**, with a maximum daily dose of 20 mg and a total dose amount of 7300 mg over a 52-week period. The trial is expected to commence recruitment on November 1, 2023, and conclude by August 22, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a history of major atherosclerotic cardiovascular disease (ASCVD) events or intermediate to high risk for ASCVD, and specific LDL-C levels. The screening will also ensure that participants are on a stable dose of lipid-lowering therapies, if applicable, for at least 30 days prior to the visit. Following the screening, participants will be randomized to receive either MK-0616 or a placebo. The trial will include follow-up visits at regular intervals to monitor efficacy and safety outcomes, with primary endpoints assessed at Week 24 and secondary endpoints at Week 52. The end-of-study visit will mark the completion of the participant's involvement in the trial.

The expected duration of participant involvement is approximately 52 weeks, with conditions for early termination including the occurrence of adverse events or discontinuation of the study intervention due to adverse events. The trial will adhere to rigorous methodological standards to ensure the reliability and validity of the findings, contributing valuable data on the potential benefits and risks of MK-0616 in managing hypercholesterolemia.

The clinical trial involves the administration of **MK-0616**, an experimental medication formulated as a **film-coated tablet**. The active substance in MK-0616 is **enlicitide chloride**, a chemical compound developed by Merck & Co. Inc. The medication is administered **orally** with a maximum daily dose of **20 mg** and a total maximum dose of **7300 mg** over a treatment period of up to **52 weeks**. The primary objective of the trial is to evaluate the efficacy and safety of MK-0616 in adults with **hypercholesterolemia**. Participants will receive the medication according to a specified dosing schedule, and compliance 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 consists of **microcrystalline cellulose, sodium chloride, and magnesium stearate**. It is designed to match the experimental medication in appearance and administration route, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is administered orally, following the same dosing schedule as the experimental medication, to maintain the study's blinding integrity.

The efficacy of MK-0616 in the treatment of **hypercholesterolemia** will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint is the percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 24. Secondary endpoints include the percent change from baseline in LDL-C at Week 52, non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and lipoprotein A [Lp(A)]. Additionally, 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, will be evaluated.

Efficacy parameters will be measured at specified timepoints, including Week 24 and Week 52, using validated laboratory tests to ensure accuracy and reliability. The data collected will be analyzed to determine the mean percent change from baseline in LDL-C and other lipid parameters, providing insights into the efficacy of MK-0616 compared to placebo. The study is designed to confirm the safety and efficacy of MK-0616 in adults with hypercholesterolemia, contributing to the understanding of its potential benefits in managing this condition.