A Study of the Safety and Efficacy of Anacetrapib (MK-0859) Among Participants With Hypercholesterolemia When Added to Ongoing Statin Therapy (MK-0859-022)

A 24-Week, Worldwide, Multicenter, Double-Blind, Randomized, Parallel, Placebo- Controlled Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Medication(s) in Patients With Hypercholesterolemia or Low HDL-C

This study will evaluate the effects of anacetrapib on low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in participants with hypercholesterolemia when added to an existing statin therapy.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Placebo; Drug: Anacetrapib

• Study Type: Interventional
• Enrollment (Actual): 589
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• If female, cannot be of reproductive potential
• Has been treated with an appropriate dose of statin for at least 6 weeks
• Coronary heart disease (CHD) or other atherosclerotic vascular disease with multiple risk factors (including diabetes, metabolic syndrome) and/or high LDL-C/low HDL-C, or needing to meet a specific LDL-C/HDL-C goal

Exclusion Criteria:

• Previously participated in a study with a cholesteryl ester transfer protein (CETP) inhibitor
• Homozygous familial hypercholesterolemia
• Severe chronic heart failure
• Uncontrolled cardiac arrhythmias, myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery by-pass graft (CABG), unstable angina, or stroke within 3 months
• Uncontrolled hypertension
• Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins
• Active or chronic hepatobiliary, hepatic, or gall bladder disease
• History of mental instability, drug/alcohol abuse within the past five years or major psychiatric illness inadequately controlled and unstable
• History of ileal bypass, gastric bypass, or other significant condition associated with malabsorption
• Human immunodeficiency virus (HIV) positive
• History of malignancy ≤5 years
• 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
• Currently taking medications that are potent inhibitors or inducers of cytochrome P450 3A4 (CYP3A) (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
• Consumes more than 2 alcoholic drinks per day
• Currently participating or has participated in a study with an investigational compound or device within 3 months
• Receiving treatment with systemic corticosteroids or taking 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; 100 mg tablet, oral, once daily for 24 weeks	Drug: Anacetrapib; Other Names: MK-0859
Placebo Comparator: Placebo; Matching tablet to Anacetrapib 100 mg, oral, once daily for 24 weeks	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baseline in LDL-C (beta-quantification [BQ] method)	Baseline and Week 24
Percent Change from Baseline in HDL-C	Baseline and Week 24
Number of Participants with Creatine Phosphokinase Elevations ≥10xULN with or without Muscle Symptoms	24 weeks
Number of Participants with Pre-specified Adjudicated Cardiovascular Serious Adverse Events or Death from Any Cause	24 weeks
Number of Participants with Significant Increase in Blood Pressure	24 weeks
Number of Participants with Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) Consecutive Elevations ≥3x Upper Limit of Normal (ULN)	24 weeks
Number of Participants with Sodium, Chloride, or Bicarbonate Elevations >ULN or Potassium Levels <Lower Limit of Normal (LLN)	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baseline in Apolipoprotein B (Apo-B)	Baseline and Week 24
Percent Change from Baseline in Apolipoprotein A-I (Apo-A-I)	Baseline and Week 24
Percent Change from Baseline in Lipoprotein(a) (lp[a])	Baseline and Week 24
Percent Change from Baseline in non-HDL-C	Baseline and Week 24
Percent Change from Baseline in HDL-C Among Participants with Low HDL-C at LDL-C Goal	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Ballantyne CM, Shah S, Sapre A, Ashraf TB, Tobias SC, Sahin T, Ye P, Dong Y, Sheu WH, Kang DH, Ferreira Rossi PR, Moiseeva Y, Briones IR, Johnson-Levonas AO, Mitchel YB. A Multiregional, Randomized Evaluation of the Lipid-Modifying Efficacy and Tolerability of Anacetrapib Added to Ongoing Statin Therapy in Patients With Hypercholesterolemia or Low High-Density Lipoprotein Cholesterol. Am J Cardiol. 2017 Aug 15;120(4):569-576. doi: 10.1016/j.amjcard.2017.03.255. Epub 2017 Apr 12.

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2013
• Primary Completion (Actual): May 29, 2015
• Study Completion (Actual): August 20, 2015

Study Registration Dates

• First Submitted: May 20, 2013
• First Submitted That Met QC Criteria: May 20, 2013
• First Posted (Estimate): May 23, 2013

Study Record Updates

• Last Update Posted (Actual): May 29, 2020
• Last Update Submitted That Met QC Criteria: May 28, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Anacetrapib
• Other Study ID Numbers: 0859-022