Randomized Study of Obicetrapib in Combination With Ezetimibe

Study Overview
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Brief Summary
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This study will be a placebo-controlled, double-blind, randomized, phase 2 study in participants with mild dyslipidemia to evaluate the efficacy, safety, and tolerability of obicetrapib and ezetimibe combination therapy.

Detailed Description
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This study will be a placebo-controlled, double-blind, randomized, phase 2 study in participants with mild dyslipidemia to evaluate the efficacy, safety, and tolerability of obicetrapib and ezetimibe combination therapy. The screening period for this study will take up to 2 weeks. Following the screening period, eligible patients will be randomized to placebo, 5 mg obicetrapib + 10 mg ezetimibe; 5 mg obicetrapib + placebo ezetimibe; or placebo obicetrapib + 10 mg ezetimibe for an 8 week treatment period. After the treatment period, patients will continue for a 4 week safety follow-up and a 8 week PK follow-up.

Official Title
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A Placebo-Controlled, Double-Blind, Randomized Phase 2 Study to Evaluate the Effect of Obicetrapib in Combination With Ezetimibe in Participants With Mild Dyslipidemia

Conditions
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Dyslipidemias, High Cholesterol, Hypercholesterolemia

Intervention / Treatment
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* Drug: Obicetrapib 5mg
* Drug: Ezetimibe 10mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understanding of the study procedures, willingness to adhere to the study schedules and diet, and agreement to participate in the study by giving written informed consent prior to Screening procedures Men or women 18 to 70 years of age, inclusive Women 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 Women of childbearing potential must have a negative urine pregnancy test at the Screening Visit. Women of childbearing potential must agree to use an effective method of avoiding pregnancy from the Screening Visit to 90 days after the last visit. Men whose partners are of childbearing potential must agree to use an effective method of avoiding pregnancy from the Screening Visit to 90 days after the last visit. Fasting LDL-C levels >2.5 mmol/L (>100 mg/dL) and <4.5 mmol/L (<175 mg/dL) and TG levels <4.5 mmol/L (<400 mg/dL) (Visit 1) and Willingness to maintain a stable diet and physical activity level throughout the study Exclusion Criteria: Body mass index >= 40 kg/m2 Participation in another clinical study involving an investigational or marketed drug within 30 days prior to the Screening Visit Currently taking any lipid-altering therapy Any clinical manifestation of atherosclerotic CVD or any evidence of ischemic coronary disease present on the 12-lead ECG at the Screening Visit Diagnosis of type 1 or type 2 diabetes mellitus; or HbA1c >= 6.5% at the Screening visit if no prior diagnosis of diabetes mellitus Uncontrolled hypertension ie, sitting systolic blood pressure >160 mmHg and/or sitting diastolic blood pressure >90 mmHg taken as the average of triplicate measurements. One retest will be allowed, at which point if the retest result is no longer exclusionary, the participant may be randomized Active muscle disease or persistent creatine kinase concentration >3 x the upper limit of normal (ULN). One retest will be allowed after 1 week to verify the result, at which point if the retest result is no longer exclusionary, the participant may be randomized History of torsades de pointes Estimated glomerular filtration rate <60 mL/min calculated using the Chronic Kidney Disease Epidemiology Collaboration equation Hepatic dysfunction as evidenced by any laboratory abnormality as follows: gamma- glutamyl transferase, alanine aminotransferase, or aspartate aminotransferase >2 x ULN, or total bilirubin >1.5 x ULN Anemia, defined as hemoglobin concentration <11 g/dL for males and hemoglobin concentration <9 g/dL for females History of malignancy within the past 5 years, with the exception of non-melanoma skin cancers Evidence of any other clinically significant non-cardiac disease or condition that, in the opinion of the Investigator, would preclude participation in the study Known ezetimibe or CETP inhibitor allergy or intolerance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>placebo obicetrapib + placebo ezetimibe; once daily | Other: Placebo<br>* tablet<br>|
| Experimental: Combination therapy<br>5 mg obicetrapib + 10 mg ezetimibe; once daily | Drug: Obicetrapib 5mg<br>* tablet<br>* Other names: CETP inhibitor;Drug: Ezetimibe 10mg<br>* tablet<br>* Other names: Antihyperlipidemic;|
| Experimental: Obicetrapib monotherapy<br>5 mg obicetrapib + placebo ezetimibe; once daily | Drug: Obicetrapib 5mg<br>* tablet<br>* Other names: CETP inhibitor;|
| Experimental: Ezetimibe monotherapy<br>placebo obicetrapib + 10 mg ezetimibe; once daily | Drug: Ezetimibe 10mg<br>* tablet<br>* Other names: Antihyperlipidemic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| obicetrapib in combination with ezetimibe compared to placebo on LDL-C | Percent change from baseline in LDL-C | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| obicetrapib monotherapy compared to placebo on LDL-C | Percent change from baseline in LDL-C | 8 weeks | 
| obicetrapib in combination with ezetimibe compared to placebo on ApoB | Percent change from baseline in ApoB | 8 weeks | 
| obicetrapib monotherapy compared to placebo on Apo-B | Percent change from baseline in Apo-B | 8 weeks | 
| obicetrapib in combination with ezetimibe compared to ezetimibe monotherapy on LDL-C | Percent change from baseline in LDL-C | 8 weeks | 
| obicetrapib monotherapy compared to ezetimibe monotherapy on LDL-C | Percent change from baseline in LDL-C | 8 weeks | 
| ezetimibe monotherapy compared to placebo on LDL-C | Percent change from baseline in LDL-C | 8 weeks | 
| obicetrapib in combination with ezetimibe compared to ezetimibe monotherapy on ApoB | Percent change from baseline in ApoB | 8 weeks | 

 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