Investigating the Effect of Obicetrapib on Lipoprotein Metabolism

Study Overview
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Brief Summary
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To determine the treatment effect with obicetrapib (10 mg) added to background statin therapy on the fractional catabolic rate (FCR) of apolipoprotein (apo) B100 in low-density lipoprotein (LDL).

Detailed Description
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The study population will comprise 20 adults, 18 to 75 years of age, who are either normolipidemic or dyslipidemic and in good health otherwise based on medical history, physical examination, vital signs and laboratory safety tests. Subjects will have plasma triglyceride level ≤ 400 mg/dL and LDL-cholesterol (LDL-C) levels ≥ 70 mg/dL and ≤ 200 mg/dL at Screening Visit and on stable Atorvastatin or Rosuvastatin for a minimum of 4 weeks.

Official Title
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A Placebo-Controlled, Phase 1 Study to Investigate the Effect of Obicetrapib on Lipoprotein Metabolism in Statin-Treated Subjects

Conditions
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Hyperlipidemias, Dyslipidemias

Intervention / Treatment
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* Drug: Obicetrapib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing to sign the Informed Consent Form. Subject is a male or female between 18 to 75 years of age. Females may be enrolled if they are not pregnant, are not breastfeeding, and do not plan on becoming pregnant during the study. Subject has a stable weight (± 3 kg) for at least 6 weeks prior to screening. Subject has a body mass index (BMI) of > 18.5 and ≤ 40 kg/m2 at the pre-study (Screening) visit. BMI is calculated by taking the subject's weight in kg and dividing it by the subject's height in meters, squared. Subject is judged to be in good health by the Study PI based on medical history, physical examination, vital sign measurements, electrocardiogram (ECG) assessments and laboratory safety tests performed at the Screening (Visit 1A) and/or prior to administration of the initial dose of study drug. Subject has fasting plasma triglyceride level ≤ 400 mg/dL, at Screening Visit 1A and is on atorvastatin or rosuvastatin for a minimum of 4 weeks, or at the Statin Optimization Visit 1B if subject has switched to, or initiated, 10 mg daily rosuvastatin for a minimum of 4 weeks. Exclusion Criteria: Subject is statin-naïve and has an LDL-C < 110 mg/dL at Screening (Visit 1A). Subject has a current or any previous history of New York Heart Association (NYHA) class III or IV heart failure or left ventricular ejection fraction < 30%. Subject has uncontrolled hypertension defined as either systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg prior to the Baseline visit, taken as the average of triplicate measurements. One triplicate retest will be allowed during the same visit, at which point if the retest result is no longer exclusionary, the subject may be randomized. Subject has an eGFR < 45 mL/min/1.73m2 at the Screening visit or history of end-stage renal disease (ESRD). Subject has active liver disease, defined as any known current infectious, neoplastic, or metabolic pathology of the liver; unexplained elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x upper limit of normal (ULN); or total bilirubin > 2 x ULN at the and/or Screening visit. Subject has a history of stroke, chronic seizures, or major neurological disorder. For subjects on thyroid hormone replacement treatment at the time of screening, there is no lower thyroid stimulating hormone (TSH) threshold for entry. The subject must have been on a stable dose of thyroid hormone therapy for ≥ 6 weeks prior to the screening. If TSH levels are undetectable and the subject requires a change in thyroid hormone therapy or this represents a new diagnosis, then the subject will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: This is a phase 1, single-site, randomized, double-blind, placebo-controlled, 2 period, fixed-sequence, pharmacodynamic study in normalipidemic or dyslipidemic subjects receiving background atorvastatin or rosuvastatin. Eligible subjects must meet all the inclusion and exclusion criteria while being on a background statin. At the Screening Visit (Visit 1A), subjects who are statin naïve or taking a different statin or another lipid lowering drug will initiate (if statin naïve), or switch to rosuvastatin 10 mg daily for a minimum of 4 weeks, at which point, LDL-C levels will be measured to determine eligibility (Statin Optimization Visit 1B). Subjects who are currently taking either atorvastatin or rosuvastatin (at any dose) at Visit 1A, can be enrolled immediately and proceed to the Baseline Kinetics Study (Visit 2A) within 1-4 weeks if all other eligibility criteria are met.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Obicetrapib placebo<br>identical matching placebo | Drug: Obicetrapib<br>* 1 tablet daily<br>* Other names: tablets;|
| Experimental: Obicetrapib 10 mg<br>10 mg tablets | Drug: Obicetrapib<br>* 1 tablet daily<br>* Other names: tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment with obicetrapib (10 mg) added to background statin therapy on the fractional catabolic rate (FCR) of apolipoprotein (apo) B100 in low-density lipoprotein (LDL). | The mean differences (obicetrapib with statin - placebo with statin) in the LDL apoB100 FCR using the baseline measure of each variable as a covariant. | 8-12 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment with obicetrapib (10 mg) added to background statin therapy on the production rate (PR) of apolipoprotein(a), or apo(a), in Lp(a). | The mean differences (obicetrapib with statin - placebo with statin) in the apo(a) in Lp(a) production rate using the baseline measure of each variable as a covariate. | 8-12 weeks |