Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)

Study Overview
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Brief Summary
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This study will evaluate the safety and effect of anacetrapib on low-density lipoprotein-cholesterol (LDL-C) when added to ongoing lipid-lowering therapy. The primary hypothesis is that treatment with anacetrapib 100 mg for 12 weeks will lower LDL-C to a greater extent than treatment with placebo.

Official Title
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A Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled, 12-Week Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Lipid-Lowering Therapy in Adult Patients With Homozygous Familial Hypercholesterolemia (HoFH)

Conditions
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Hyperlipoproteinemia Type II, Homozygous Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: Anacetrapib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with HoFH by genotyping If female, cannot be of reproductive potential Have been stabilized on statin monotherapy or statin therapy coadministered with other lipid medications for at least 6 weeks Exclusion Criteria: Severe chronic heart failure defined by New York Heart Association (NYHA) Classes III or IV Uncontrolled cardiac arrhythmias, myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary arterial by-pass graft (CABG), unstable angina or stroke within 3 months prior to Visit 1 or has planned procedures scheduled within first 12 weeks of study Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins Active or chronic hepatobiliary or gall bladder disease History of ileal bypass, gastric bypass, or other significant condition associated with malabsorption Human immunodeficiency virus (HIV) positive Donated blood products or has had phlebotomy of >300 mL within 8 weeks or intends to donate 250_mL of blood products or receive blood products within the projected duration of the study Taking medications that are potent inhibitors or inducers of cytochrome P450 3A4 (CYP3A4), including but not limited to cyclosporine, systemic itraconazole or ketoconazole, erythromycin, clarithromycin, or telithromycin, nefazodone, protease inhibitors, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St John's wort) or has discontinued treatment <3 weeks prior. Consumption of >1 liter of grapefruit juice per day is also prohibited. Currently participating or has participated in a study with an investigational compound or device within 3 months Consume more than 2 alcoholic drinks per day Receiving treatment with systemic corticosteroids or systemic anabolic agents

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anacetrapib<br>Participants receive anacetrapib 100 mg orally once daily for 12 weeks. | Drug: Anacetrapib<br>* 100 mg tablet orally, once daily for 12 weeks<br>* Other names: MK-0859;|
| Placebo Comparator: Placebo<br>Participants receive placebo orally once daily for 12 weeks. | Drug: Placebo<br>* Placebo for anacetrapib orally, once daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from Baseline in Low-density Lipoprotein-Cholesterol (LDL-C) using beta-quantification method |  | Baseline and Week 12 | 
| Number of Participants with Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) Consecutive Elevations ≥3x Upper Limit of Normal (ULN) |  | 12 weeks | 
| Number of Participants with Creatine Phosphokinase Elevations ≥10xULN with or without Muscle Symptoms |  | 12 weeks | 
| Number of Participants with Sodium, Chloride, or Bicarbonate Elevations >ULN or Potassium Levels <Lower Limit of Normal (LLN) |  | 12 weeks | 
| Number of Participants with Pre-specified Adjudicated Cardiovascular Serious Adverse Events or Death from Any Cause |  | 12 weeks | 
| Number of Participants with Significant Increase in Blood Pressure |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in High-density Lipoprotein-cholesterol (HDL-C) |  | Baseline and Week 12 | 
| Percent Change from Baseline in Apolipoprotein A-I (apoA-I) |  | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HoFH