randomized study to evaluate the effect of obicetrapib on top of maximum tolerated lipid-modifying therapies

Conditions: Dyslipidemias; High Cholesterol; Hypercholesterolemia; Familial Hypercholesterolemia; Atherosclerotic Cardiovascular Disease

Summary: 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

Keywords: obicetrapib broadway cholesteryl ester transfer protein (cetp) inhibitor heterozygous familial hypercholesterolemia (hefh) atherosclerotic cardiovascular disease (ascvd)