Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies

Study Overview
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Brief Summary
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The study is a placebo-controlled, double-blind, randomized, phase 3 study in participants with heterozygous familial hypercholesterolemia (HeFH) and/or atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors to evaluate the efficacy, safety and tolerability of obicetrapib 10mg and ezetimibe 10mg fixed dose combination as an adjunct to diet and maximally tolerated lipid-lowering therapy.

Detailed Description
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This study will be a placebo-controlled, double-blind, randomized, phase 3 study in participants with heterozygous familial hypercholesterolemia (HeFH) and/or atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors 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 14 days. Afterwards patients will be randomized 1:1:1:1 to Obicetrapib 10 mg and ezetimibe 10 mg fixed dose combination, obicetrapib 10 mg, ezetimibe 10 mg or placebo for a 84 day treatment period. After the treatment period, patients will have an end of study follow-up visit.

Official Title
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A Placebo-Controlled, Double-Blind, Randomized, Phase 3 Study to Evaluate the Effect of Obicetrapib 10 mg and Ezetimibe 10 mg Fixed Dose Combination Daily on Top of Maximally Tolerated Lipid-Modifying Therapy in Participants With Heterozygous Familial Hypercholesterolemia (HeFH) and/or Atherosclerotic Cardiovascular Disease (ASCVD) or Multiple ASCVD Risk Factors

Conditions
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Dyslipidemias, Hypercholesterolemia, Familial Hypercholesterolemia, ASCVD, High Cholesterol

Intervention / Treatment
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* Combination Product: Combination Therapy
* Drug: Monotherapy obicetrapib
* Drug: Monotherapy ezetimibe
* Other: Combination Therapy placebo
* Other: Obicetrapib Placebo
* Other: Ezetimibe Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have underlying HeFH and/or a history of ASCVD or multiple ASCVD risk factors On maximally tolerated lipid-modifying therapy as an adjunct to a diet and lifestyle modifications LDL-C ≥ 70 mg/dL or HDL-C ≥ 100 mg/dL Triglycerides < 500 Estimated glomerular filtration rate ≥ 15 mL/min/1.73 m2 Exclusion Criteria: History of New York Heart Association (NYHA) class III or IV heart failure of left ventricular ejection fraction <30% Hospitalized for heart failure within the last 5 years Myocardial infarction, stroke, non-elective coronary revascularization or hospitalization for unstable angina or chest pain in the last 3 months Uncontrolled severe hypertension Diagnosis of homozygous FH Liver disease HbA1c ≥ 10.0% or fasting glucose ≥ 270 mg/dL Thyroid-stimulating hormone >1.5 x upper limit of normal (ULN) History of malignancy Creatinine kinase (CK) >3 X ULN Alcohol abuse Treatment with investigational product Treatment with gemfibrozil or ezetimibe Previous participation in a trial evaluating obicetrapib Known allergy to study drugs, placebo or excipients in study drugs of placebo Other condition that would interfere with the conduct of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo-controlled, double blind, randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination Therapy<br>once-daily obicetrapib 10 mg and ezetimibe 10 mg fixed dose combination tablet, placebo tablet, placebo capsule | Combination Product: Combination Therapy<br>* tablet; 10mg obicetrapib and 10mg ezetimibe fixed does combination<br>* Other names: ezetimibe;Other: Obicetrapib Placebo<br>* tablet; no active ingredient<br>Other: Ezetimibe Placebo<br>* capsule; no active ingredient<br>|
| Experimental: Monotherapy obicetrapib<br>once-daily obicetrapib 10 mg, placebo tablet, placebo capsule | Drug: Monotherapy obicetrapib<br>* tablet; 10mg obicetrapib<br>* Other names: CETP inhibitor;Other: Combination Therapy placebo<br>* tablet; no active ingredient<br>Other: Ezetimibe Placebo<br>* capsule; no active ingredient<br>|
| Active Comparator: Monotherapy ezetimibe<br>once-daily ezetimibe 10 mg capsule, 2 placebo tablets | Drug: Monotherapy ezetimibe<br>* capsule; 10mg ezetimibe<br>Other: Combination Therapy placebo<br>* tablet; no active ingredient<br>Other: Obicetrapib Placebo<br>* tablet; no active ingredient<br>|
| Placebo Comparator: Placebo<br>once-daily placebo tablets (2), placebo capsule | Other: Combination Therapy placebo<br>* tablet; no active ingredient<br>Other: Obicetrapib Placebo<br>* tablet; no active ingredient<br>Other: Ezetimibe Placebo<br>* capsule; no active ingredient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of combination therapy compared to placebo on LDL-C | Percent Change in LDL-C | 84-Days | 
| Effect of combination therapy compared to ezetimibe 10 mg monotherapy on LDL-C | Percent Change in LDL-C | 84-Days | 
| Effect of combination therapy compared to obicetrapib 10 mg monotherapy on LDL-C | Percent Change in LDL-C | 84-Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of combination therapy compared to placebo on non-HDL-C | Percent Change in non-HDL-C | 84-Days | 
| Effect of combination therapy compared compared to ezetimibe 10 mg monotherapy on non-HDL-C | Percent Change in non-HDL-C | 84-Days | 
| Effect of combination therapy compared to obicetrapib 10 mg monotherapy on non-HDL-C | Percent Change in non-HDL-C | 84-Days | 
| Effect of combination therapy compared to placebo on Apolipoprotein B (ApoB) | Percent Change in ApoB | 84-Days | 
| Effect of combination therapy compared to ezetimibe 10 mg monotherapy on ApoB | Percent Change in ApoB | 84-Days | 
| Effect of combination therapy compared to obicetrapib 10 mg monotherapy on ApoB | Percent Change in ApoB | 84-Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obicetrapib, statin, LDL-C, cholesterol, atherosclerosis