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

Phase 3
Terminated
Conditions
Homozygous Familial Hypercholesterolemia
Hyperlipoproteinemia Type II
Interventions
Drug: Placebo
Registration Number
NCT01841684
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
2
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants receive placebo orally once daily for 12 weeks.
AnacetrapibAnacetrapibParticipants receive anacetrapib 100 mg orally once daily for 12 weeks.
Primary Outcome Measures
NameTimeMethod
Percent change from Baseline in Low-density Lipoprotein-Cholesterol (LDL-C) using beta-quantification methodBaseline 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 Symptoms12 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 Cause12 weeks
Number of Participants with Significant Increase in Blood Pressure12 weeks
Secondary Outcome Measures
NameTimeMethod
Percent Change from Baseline in Apolipoprotein A-I (apoA-I)Baseline and Week 12
Percent Change from Baseline in High-density Lipoprotein-cholesterol (HDL-C)Baseline and Week 12
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