Hyperlipoproteinemia Type II, Homozygous Familial Hypercholesterolemia
Conditions
Keywords
HoFH
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.
Interventions
DRUGAnacetrapib
100 mg tablet orally, once daily for 12 weeks
DRUGPlacebo
Placebo for anacetrapib orally, once daily for 12 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Significant Increase in Blood Pressure | 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 |
| 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Outcome results
None listed