Clinical trial NCT01524289: Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
Official title: A 1-Year, Worldwide, Multicenter, Double-Blind, Randomized, Parallel, Placebo-Controlled Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Medication(s) in Patients With Heterozygous Familial Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperlipoproteinemia Type II
Hypercholesterolemia, Familial
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-02-01
Enrollment: 306
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the efficacy and tolerability of adding anacetrapib to ongoing statin therapy in participants with heterozygous familial hypercholesterolemia (HeFH).


Eligibility criteria: Inclusion Criteria:

* If of reproductive potential, must agree to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control for the duration of the study
* Diagnosed with Heterozygous Familial Hypercholesterolemia (HeFH)
* Have been treated with an optimal dose of statin for at least 6 weeks

Exclusion Criteria:

* Received treatment with low-density lipoprotein (LDL) apheresis within 4 weeks of screening or expect to undergo treatment with LDL apheresis during the course of the study
* Homozygous familial hypercholesterolemia
* Severe chronic heart failure
* Uncontrolled hypertension
* Uncontrolled cardiac arrhythmias, myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), unstable angina, or stroke within 3 months
* Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins
* Active or chronic hepatobiliary, hepatic, or gall bladder disease
* Pregnant or breast-feeding, or plans to become pregnant during the study or within 2 years after stopping study medication
* History of ileal bypass, gastric bypass, or other significant condition associated with malabsorption
* Human immunodeficiency virus (HIV) positive
* History of malignancy ≤5 years
* 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
* Currently taking medications that are potent inhibitors or inducers of cytochrome P450 3A4 (CYP3A) (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
* Consumes more than 2 alcoholic drinks per day
* Currently participating or has participated in a study with an investigational compound or device within 3 months
* Receiving treatment with systemic corticosteroids or taking systemic anabolic agents

Primary outcomes:
measure: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) - Treatment Phase
timeFrame: Baseline and Week 52
measure: Percentage of Participants With Any Adverse Event - Treatment Phase
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Any Treatment-Related Adverse Event - Treatment Phase
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Any Serious Adverse Event - Treatment Phase
timeFrame: Up to 52 weeks
measure: Percentage of Participants Discontinuing Study Treatment Due to an Adverse Event - Treatment Phase
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Changes in Systolic Blood Pressure (SBP) >= 10 mm Hg
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Changes in SBP >= 15 mm Hg
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Changes in Diastolic Blood Pressure (DBP) >= 10 mm Hg
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Sodium Levels > Upper Limit of Normal (ULN)
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Chloride Levels > ULN
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Potassium Levels < Lower Limit of Normal (LLN)
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Bicarbonate Levels > ULN
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Consecutive Changes in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x ULN
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Creatine Kinase (CK) Level >=10 x ULN
timeFrame: Up to 52 weeks
measure: Percentage of Participants With CK Level >=10 x ULN With Muscle Spasms
timeFrame: Up to 52 weeks
measure: Percentage of Participants Adjudicated Cardiovascular (CV) SAE
timeFrame: Up to 52 weeks
measure: Percentage of Participants Who Died From Any Cause - Treatment Phase
timeFrame: Up to 52 weeks
Secondary outcomes:
measure: Percent Change From Baseline in High-Density Lipoprotein Cholesterol Levels
timeFrame: Baseline and Week 52
measure: Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol Levels
timeFrame: Baseline and Week 52
measure: Percent Change From Baseline in Apolipoprotein (Apo) B Levels
timeFrame: Baseline and Week 52
measure: Percent Change From Baseline in Apolipoprotein (Apo) A-1 Levels
timeFrame: Baseline and Week 52
measure: Percent Change From Baseline in Lipoprotein(a) (Lp[a]) Levels
timeFrame: Baseline and Week 52
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Kastelein JJ, Besseling J, Shah S, Bergeron J, Langslet G, Hovingh GK, Al-Saady N, Koeijvoets M, Hunter J, Johnson-Levonas AO, Fable J, Sapre A, Mitchel Y. Anacetrapib as lipid-modifying therapy in patients with heterozygous familial hypercholesterolaemia (REALIZE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet. 2015 May 30;385(9983):2153-61. doi: 10.1016/S0140-6736(14)62115-2. Epub 2015 Mar 3.