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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia
• Intervention / Treatment: Drug: Anacetrapib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: April 24, 2013
• First Submitted That Met QC Criteria: April 25, 2013
• First Posted (Estimate): April 26, 2013

Study Record Updates

• Last Update Posted (Estimate): June 1, 2015
• Last Update Submitted That Met QC Criteria: May 29, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: HoFH
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hypercholesterolemia; Hyperlipidemias; Hyperlipoproteinemia Type II; Hyperlipoproteinemias; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Anacetrapib
• Other Study ID Numbers: 0859-042; 2012-002434-37 (EudraCT Number)