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

Homozygous Familial Hypercholesterolemia Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01841684
• Other study ID #: 0859-042
• Secondary ID: 2012-002434-37
• Status: Terminated
• Phase: Phase 3
• First received: April 24, 2013
• Last updated: May 29, 2015
• Start date: June 2013
• Est. completion date: June 2014

Study information

• Verified date: May 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Homozygous Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II
• Hyperlipoproteinemias

Intervention

Drug:
• Anacetrapib
100 mg tablet orally, once daily for 12 weeks
• Placebo
Placebo for anacetrapib orally, once daily for 12 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change from Baseline in Low-density Lipoprotein-Cholesterol (LDL-C) using beta-quantification method		Baseline and Week 12	No
Primary	Number of Participants with Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) Consecutive Elevations =3x Upper Limit of Normal (ULN)		12 weeks	Yes
Primary	Number of Participants with Creatine Phosphokinase Elevations =10xULN with or without Muscle Symptoms		12 weeks	Yes
Primary	Number of Participants with Sodium, Chloride, or Bicarbonate Elevations >ULN or Potassium Levels <Lower Limit of Normal (LLN)		12 weeks	Yes
Primary	Number of Participants with Pre-specified Adjudicated Cardiovascular Serious Adverse Events or Death from Any Cause		12 weeks	Yes
Primary	Number of Participants with Significant Increase in Blood Pressure		12 weeks	Yes
Secondary	Percent Change from Baseline in High-density Lipoprotein-cholesterol (HDL-C)		Baseline and Week 12	No
Secondary	Percent Change from Baseline in Apolipoprotein A-I (apoA-I)		Baseline and Week 12	No