Evaluation of the Safety and Efficacy of Enlicitide Chloride (MK-0616) in an Open-Label Extension Study for Adults with Hypercholesterolemia

The primary objective of this Phase 3, open-label extension study is to evaluate the **safety** and tolerability of enlicitide treatment in adults with **hypercholesterolemia**. This is clinically relevant as it aims to ensure that the treatment is safe for long-term use, which is crucial for managing chronic conditions such as high cholesterol.

Secondary objectives include: - Evaluating the efficacy of enlicitide on the percent change from baseline in LDL-C at Week 8 of the open-label extension (OLE). - Assessing the efficacy on percent change from baseline in non-HDL-C, ApoB, and Lp(a) at Week 8 of the OLE. - Determining the efficacy on the proportion of participants achieving LDL-C levels of <70 mg/dL and <55 mg/dL with a ≥50% reduction from baseline over time. These secondary objectives are important for understanding the potential of enlicitide to improve lipid profiles and reduce cardiovascular risk in patients with hypercholesterolemia.

The clinical trial involves a total of **2870 participants** who have been selected based on their completion of a prior enlicitide study, with a compliance rate of at least 80%. The study population includes both **male and female subjects** and spans an **age range** that includes adults and older adults. Participants are not considered part of a vulnerable population. The trial focuses on individuals with **hypercholesterolemia**, a condition characterized by elevated cholesterol levels in the blood. The selection criteria ensure that participants have previously engaged in related studies, thereby maintaining a consistent study population. Lifestyle factors such as diet and physical activity are not specified, and the trial does not impose additional lifestyle modifications on participants. The primary objective of the trial is to evaluate the safety and tolerability of enlicitide treatment.

The clinical trial is a **Phase 3, open-label extension study** designed to evaluate the safety and efficacy of **MK-0616** in adults with **hypercholesterolemia**. The trial is structured to follow participants who have completed a prior study involving **enlicitide chloride**. The primary objective is to assess the safety and tolerability of the treatment, with primary endpoints including the number of participants experiencing adverse events and those discontinuing the study drug due to adverse events. Secondary endpoints focus on the percent change from baseline in various cholesterol-related measures at Week 8 of the extension study.

The trial employs a **randomized, controlled** design, ensuring that the results are scientifically robust and reliable. Participants will be involved in the study for a maximum treatment period of 1095 days, with the trial estimated to conclude by October 2028. The study will commence recruitment in October 2024. Participants are required to have completed a previous **enlicitide** study with at least 80% compliance to be eligible for inclusion. There are no specific exclusion criteria listed.

Study visits are sequenced to include an initial screening visit to confirm eligibility based on prior study completion and compliance. Follow-up visits will occur at regular intervals to monitor safety and efficacy outcomes, with specific assessments conducted at Week 8. The end-of-study visit will finalize data collection and ensure participant safety post-treatment. Participants may be terminated early from the study if they experience significant adverse events or fail to adhere to the study protocol.

The clinical trial involves the administration of the experimental medication **MK-0616**, which is a **film-coated tablet** containing the active substance **enlicitide chloride**. The pharmaceutical form of the medication is designed for **oral use**. The maximum daily dose of MK-0616 is 20 mg, with a total maximum dose of 21,900 mg over the course of the study. The treatment period extends up to 1,095 days. The medication is produced by Merck & Co. Inc. and is not formulated for pediatric use. The chemical origin of the active substance is noted, and the medication is classified as a non-orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the safety and tolerability of enlicitide treatment in adults with hypercholesterolemia. Participants' compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

The efficacy of the clinical trial evaluating MK-0616, a **film-coated tablet** containing **enlicitide chloride**, will be assessed through several primary and secondary endpoints. The primary endpoints focus on safety, specifically the number of participants experiencing one or more adverse events (AEs) and the number of participants who discontinue the study drug due to an AE. Secondary endpoints are designed to measure the efficacy of the treatment in terms of lipid profile improvements. These include the percent change from baseline of the parent study in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]) at Week 8 of this extension study. Additionally, the percentage of participants achieving LDL-C levels of less than 70 mg/dL and 55 mg/dL, with at least a 50% reduction from baseline of the parent study, will be evaluated.

The efficacy parameters will be collected and analyzed at specific timepoints, with a key assessment occurring at Week 8 of the extension study. The trial is structured as an open-label extension study, allowing for the continuous evaluation of the safety and efficacy of MK-0616 in adults with hypercholesterolemia. The study aims to confirm the safety and efficacy of the treatment in the target population, contributing to the overall understanding of its therapeutic potential.