Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies

This study will be a placebo-controlled, double-blind, randomized, phase 3 study in participants with underlying heterozygous familial hypercholesterolemia (HeFH) and/or ASCVD to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to diet and maximally tolerated lipid-lowering therapy

This study will be a placebo-controlled, double-blind, randomized, phase 3 study in participants with underlying HeFH and/or ASCVD to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to diet and maximally tolerated lipid-lowering therapy. The screening period for this study will take up to 28 days. Afterwards patients will be randomized to placebo or 10 mg obicetrapib for a 365 day treatment period. After the treatment period, patients will have an end of study follow-up visit.

Eligibility Criteria:
Inclusion Criteria:

* Females may be enrolled if all 3 of the following criteria are met:
* They are not pregnant;
* They are not breastfeeding; and
* They do not plan on becoming pregnant during the study;
* Have underlying heterozygous familial hypercholesterolemia (HeFH) and/or a history of established ASCVD
* Are on maximally tolerated lipid-modifying therapy as an adjunct to a lipid-lowering diet and other lifestyle modifications, defined as follows:
* A statin at a maximally tolerated stable dose for at least 8 weeks prior to Screening
* Atorvastatin 40 and 80 mg; and
* Rosuvastatin 20 and 40 mg;
* Ezetimibe with or without maximally tolerated statin for at least 8 weeks prior to Screening
* Bempedoic acid with a maximally tolerated statin for at least 8 weeks prior to Screening
* A PCSK-9 targeted therapy alone or in combination with other lipid-modifying therapy for at least 4 stable doses prior to Screening
* Have a fasting serum LDL-C at Screening as follows:
* Fasting serum LDL-C ≥ 55 to \< 100 mg/dL (≥1.4 to \<2.6 mmol/L) OR non-HDL-C ≥85 mg/dL (≥2.2 mmol/L) to \< 130 mg/dL (\<3.4 mmol/L) with at least 1 of the following risk enhancers at Screening;
* Recent MI (\> 3 and \< 12 months prior to Randomization);
* Type 2 diabetes mellitus;
* Current daily cigarette smoking;
* Age of \> 60 years;
* High sensitivity C-reactive protein (hsCRP) ≥2.0 mg/L (≥19.0 nmol/L) at Screening or within 6 months prior to Screening
* Fasting triglycerides (TG) \> 150 mg/dL (\>1.7 mmol/L);
* Fasting lipoprotein (a) \> 30 mg/dL (\>70 nmol/L); and/or
* Fasting HDL-C \< 40 mg/dL (\<1.0 mmol/L); OR
* Fasting serum LDL-C ≥ 100 mg/dL (≥2.6 mmol/L) or non-HDL-C ≥130 mg/dL (≥3.4 mmol/L)
* Fasting triglyceride (TG) \< 500 mg/dL (\<5.7 mmol/L) at Screening; and
* Have an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 at Screening

Exclusion Criteria:

* New York Heart Association class III or IV heart failure or left ventricular ejection fraction \< 30%;
* Hospitalized for heart failure within 5 years prior to Screening
* Major adverse cardiac event (MACE) within 3 months prior to Screening;
* Uncontrolled severe hypertension, defined as either systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥100 mmHg prior to Randomization;
* Formal diagnosis of homozygous familial hypercholesterolemia (HoFH);
* Active liver disease;
* HbA1c ≥10% or a fasting glucose ≥270 mg/dL (≥15.0 mmol/L) at Screening;
* Thyroid-stimulating hormone \>1.5 X upper limit of normal (ULN) at Screening;
* Creatine kinase \> 3 X upper limit of normal (ULN) at Screening;
* History of malignancy that required surgery (excluding local and wide local excision), radiation therapy, and/or systemic therapy during the 3 years prior to Randomization;
* Known history of alcohol and/or drug abuse within 5 years prior to Randomization
* Received treatment with other investigational products or devices within 30 days of Screening or 5 half-lives of the previous investigational product, whichever is longer;
* Are taking gemfibrozil or have taken gemfibrozil within 30 days of Screening
* Planned use of other investigational products or devices during the course of the study;
* Participated in any clinical trial evaluating obicetrapib; or
* Known allergy or hypersensitivity to obicetrapib, placebo, or any of the excipients in obicetrapib or placebo
* Any condition that, according to the Investigator, could interfere with the conduct of the study