Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
Primary Purpose
Hyperlipoproteinemia Type II, Homozygous Familial Hypercholesterolemia
Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Anacetrapib
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hyperlipoproteinemia Type II focused on measuring HoFH
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Anacetrapib
Placebo
Arm Description
Participants receive anacetrapib 100 mg orally once daily for 12 weeks.
Participants receive placebo orally once daily for 12 weeks.
Outcomes
Primary Outcome Measures
Percent change from Baseline in Low-density Lipoprotein-Cholesterol (LDL-C) using beta-quantification method
Number of Participants with Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) Consecutive Elevations ≥3x Upper Limit of Normal (ULN)
Number of Participants with Creatine Phosphokinase Elevations ≥10xULN with or without Muscle Symptoms
Number of Participants with Sodium, Chloride, or Bicarbonate Elevations >ULN or Potassium Levels <Lower Limit of Normal (LLN)
Number of Participants with Pre-specified Adjudicated Cardiovascular Serious Adverse Events or Death from Any Cause
Number of Participants with Significant Increase in Blood Pressure
Secondary Outcome Measures
Percent Change from Baseline in High-density Lipoprotein-cholesterol (HDL-C)
Percent Change from Baseline in Apolipoprotein A-I (apoA-I)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01841684
Brief Title
Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2015
Overall Recruitment Status
Terminated
Study Start Date
June 2013 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
June 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperlipoproteinemia Type II, Homozygous Familial Hypercholesterolemia
Keywords
HoFH
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Anacetrapib
Arm Type
Experimental
Arm Description
Participants receive anacetrapib 100 mg orally once daily for 12 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants receive placebo orally once daily for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Anacetrapib
Other Intervention Name(s)
MK-0859
Intervention Description
100 mg tablet orally, once daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo for anacetrapib orally, once daily for 12 weeks
Primary Outcome Measure Information:
Title
Percent change from Baseline in Low-density Lipoprotein-Cholesterol (LDL-C) using beta-quantification method
Time Frame
Baseline and Week 12
Title
Number of Participants with Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) Consecutive Elevations ≥3x Upper Limit of Normal (ULN)
Time Frame
12 weeks
Title
Number of Participants with Creatine Phosphokinase Elevations ≥10xULN with or without Muscle Symptoms
Time Frame
12 weeks
Title
Number of Participants with Sodium, Chloride, or Bicarbonate Elevations >ULN or Potassium Levels <Lower Limit of Normal (LLN)
Time Frame
12 weeks
Title
Number of Participants with Pre-specified Adjudicated Cardiovascular Serious Adverse Events or Death from Any Cause
Time Frame
12 weeks
Title
Number of Participants with Significant Increase in Blood Pressure
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Percent Change from Baseline in High-density Lipoprotein-cholesterol (HDL-C)
Time Frame
Baseline and Week 12
Title
Percent Change from Baseline in Apolipoprotein A-I (apoA-I)
Time Frame
Baseline and Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
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