A Study of the Safety and Efficacy of Anacetrapib (MK-0859) When Added to Ongoing Statin Therapy (MK-0859-021)

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 2 different dose levels 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-modifying therapy.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Anacetrapib 100 mg; Drug: Placebo for anacetrapib 25 mg; Drug: Placebo for anacetrapib 100 mg; Drug: Anacetrapib 25 mg

• Study Type: Interventional
• Enrollment (Actual): 459
• 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
• Have been treated with an optimal 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
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo for anacetrapib 25 mg; Placebo tablet, orally, once daily for 24 weeks; Drug: Placebo for anacetrapib 100 mg; Placebo tablet, orally, once daily for 24 weeks
Experimental: Anacetrapib 100 mg	Drug: Anacetrapib 100 mg; 100 mg tablet, oral, once daily for 24 weeks; Other Names: MK-0859; Drug: Placebo for anacetrapib 25 mg; Placebo tablet, orally, once daily for 24 weeks
Experimental: Anacetrapib 25 mg	Drug: Placebo for anacetrapib 100 mg; Placebo tablet, orally, once daily for 24 weeks; Drug: Anacetrapib 25 mg; 25 mg tablet, oral, once daily for 24 weeks; Other Names: MK-0859

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 Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) Consecutive Elevations ≥3xULN (Upper Limit of Normal)	24 Weeks
Number of Participants with Creatine Phosphokinase Elevations ≥10xULN with or without Muscle Symptoms	24 weeks
Number of Participants with Sodium, Chloride, or Bicarbonate Elevations >ULN or Potassium Levels <LLN (Lower Limit of Normal)	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

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 non-HDL-C	Baseline and Week 24
Percent Change from Baseline in Lipoprotein(a) (lp[a])	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, Kher U, Hunter JA, Gill GG, Cressman MD, Ashraf TB, Johnson-Levonas AO, Mitchel YB. 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 Feb 1;119(3):388-396. doi: 10.1016/j.amjcard.2016.10.032. Epub 2016 Nov 1.

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2012
• Primary Completion (Actual): October 29, 2014
• Study Completion (Actual): October 29, 2014

Study Registration Dates

• First Submitted: October 26, 2012
• First Submitted That Met QC Criteria: October 26, 2012
• First Posted (Estimate): October 30, 2012

Study Record Updates

• Last Update Posted (Actual): April 17, 2017
• Last Update Submitted That Met QC Criteria: April 13, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Protein Synthesis Inhibitors; Oxazolidinones; Anacetrapib
• Other Study ID Numbers: 0859-021; 2012-003110-14 (EudraCT Number)