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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)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01841684
First received: April 24, 2013
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Hyperlipoproteinemia Type II
Homozygous Familial Hypercholesterolemia
Drug: Anacetrapib
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled, 12-Week Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Lipid-Lowering Therapy in Adult Patients With Homozygous Familial Hypercholesterolemia (HoFH)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percent change from Baseline in Low-density Lipoprotein-Cholesterol (LDL-C) using beta-quantification method [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Number of Participants with Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) Consecutive Elevations ≥3x Upper Limit of Normal (ULN) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Number of Participants with Creatine Phosphokinase Elevations ≥10xULN with or without Muscle Symptoms [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Number of Participants with Sodium, Chloride, or Bicarbonate Elevations >ULN or Potassium Levels <Lower Limit of Normal (LLN) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Number of Participants with Pre-specified Adjudicated Cardiovascular Serious Adverse Events or Death from Any Cause [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Number of Participants with Significant Increase in Blood Pressure [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percent Change from Baseline in High-density Lipoprotein-cholesterol (HDL-C) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change from Baseline in Apolipoprotein A-I (apoA-I) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: June 2013
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anacetrapib
Participants receive anacetrapib 100 mg orally once daily for 12 weeks.
Drug: Anacetrapib
100 mg tablet orally, once daily for 12 weeks
Other Name: MK-0859
Placebo Comparator: Placebo
Participants receive placebo orally once daily for 12 weeks.
Drug: Placebo
Placebo for anacetrapib orally, once daily for 12 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01841684     History of Changes
Other Study ID Numbers: 0859-042, 2012-002434-37
Study First Received: April 24, 2013
Last Updated: June 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
HoFH

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipoproteinemias
Dyslipidemias
Genetic Diseases, Inborn
Hyperlipidemias
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Metabolic Diseases
Metabolism, Inborn Errors
Anacetrapib
Oxazolidinones
Anti-Infective Agents
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Synthesis Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014