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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Hypercholesterolemia

Intervention / Treatment
-----------------
* Drug: Anacetrapib 100 mg
* Drug: Placebo for anacetrapib 100 mg
* Drug: Anacetrapib 25 mg
* Drug: Placebo for anacetrapib 25 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from Baseline in non-HDL-C |  | Baseline and Week 24 | 
| 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 HDL-C Among Participants with Low HDL-C at LDL-C goal |  | Baseline and Week 24 |