Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)

NCT01524289 | Completed Phase 3 Results

• 3 other identifiers: 0859-0202011-004525-27MK-0859-020
• Study Type: interventional
• Target: 306
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Hyperlipoproteinemia Type II; Hypercholesterolemia, Familial

Outcome Measures

Primary Outcomes (17)

• Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) - Treatment Phase

  LDL-C levels were measured at baseline and week 52 (or at discontinuation) using a beta quantification method. The Treatment Phase was the period from the date of the participant's first dose of study treatment (randomization visit, Visit 3) to the participant's last visit on treatment (discontinuation visit or Visit 8 \[Week 52\]).

  Baseline and Week 52

• Percentage of Participants With Any Adverse Event - Treatment Phase

  An adverse event (AE) or experience was any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a study treatment, whether or not considered related to the use of the study treatment. Any worsening of a preexisting condition which was temporally associated with the use of the study treatment is also an AE. The percentage of participants with any adverse event during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants With Any Treatment-Related Adverse Event - Treatment Phase

  An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of the treatment. Any worsening of a preexisting condition which was temporally associated with the use of the study treatment was also an AE. AEs reported by the investigator as definitely, probably or possibly related to study treatment were considered treatment-related. The percentage of participants with any treatment-related adverse event during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants With Any Serious Adverse Event - Treatment Phase

  A serious adverse experience (SAE) was any adverse event that occurred at any dose that resulted in death or was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, or was a congenital anomaly/birth defect. The percentage of participants with any serious adverse event during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants Discontinuing Study Treatment Due to an Adverse Event - Treatment Phase

  An adverse event (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of the drug. Any worsening of a preexisting condition which was temporally associated with the use of the study drug was also an AE. The percentage of participants who discontinued study treatment due to an AE during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants With Changes in Systolic Blood Pressure (SBP) >= 10 mm Hg

  Participants had SBP assessed at baseline and throughout the 52-week treatment period. Percentage of participants who had a SBP reading that was \>= 10 mm Hg higher than their baseline SBP for any assessment performed during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants With Changes in SBP >= 15 mm Hg

  Participants had SBP assessed at baseline and throughout the 52-week treatment period. The percentage of participants who had a SBP reading that was \>= 15 mm Hg higher than their baseline SBP for any assessment performed during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants With Changes in Diastolic Blood Pressure (DBP) >= 10 mm Hg

  Participants had DBP assessed at baseline and throughout the 52-week treatment period. The percentage of participants who had a DBP reading that was \>= 10 mm Hg higher than their baseline DBP for any assessment performed during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants With Sodium Levels > Upper Limit of Normal (ULN)

  Participants had sodium levels assessed throughout the 52-week treatment period. The percentage of participants who had any sodium level that was greater than the ULN of 145 mEq/L during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants With Chloride Levels > ULN

  Participants had chloride levels assessed throughout the 52-week treatment period. The percentage of participants who had any chloride level that was \> the ULN of 110 mEq/L during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants With Potassium Levels < Lower Limit of Normal (LLN)

  Participants had potassium levels assessed throughout the 52-week treatment period. The percentage of participants who had any potassium level that was \< the LLN of 3.5 mEq/L during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants With Bicarbonate Levels > ULN

  Participants had bicarbonate levels assessed throughout the 52-week treatment period. The percentage of participants who had any bicarbonate level that was \> the ULN of 33 mEq/L during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants With Consecutive Changes in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x ULN

  Participants had AST and ALT levels assessed throughout the 52-week treatment period. The percentage of participants who had 2 consecutive assessments of either AST or ALT that were 3 x ULN or greater during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants With Creatine Kinase (CK) Level >=10 x ULN

  Participants had CK levels assessed throughout the 52-week treatment period. The percentage of participants who had any CK level that was \>=10 x ULN during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants With CK Level >=10 x ULN With Muscle Spasms

  Participants had CK levels assessed throughout the 52-week treatment period. The percentage of participants who had any CK level that was \>=10 x ULN and had associated muscle spasms during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants Adjudicated Cardiovascular (CV) SAE

  An AE or suspected adverse reaction was considered an SAE if it resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. All events were adjudicated by an expert committee independent of the Sponsor. The percentage of participants that experienced adjudicated SAEs of CV death, non-fatal stroke, non-fatal myocardial infarction, or unstable angina during the treatment phase is presented.

  Up to 52 weeks

• Percentage of Participants Who Died From Any Cause - Treatment Phase

  The percentage of participants who died from any cause during the treatment phase is presented. All deaths were adjudicated by an expert committee independent of the Sponsor.

  Up to 52 weeks

Secondary Outcomes (5)

• Percent Change From Baseline in High-Density Lipoprotein Cholesterol Levels

  Baseline and Week 52

• Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol Levels

  Baseline and Week 52

• Percent Change From Baseline in Apolipoprotein (Apo) B Levels

  Baseline and Week 52

• Percent Change From Baseline in Apolipoprotein (Apo) A-1 Levels

  Baseline and Week 52

• Percent Change From Baseline in Lipoprotein(a) (Lp[a]) Levels

  Baseline and Week 52

Study Arms (2)

Anacetrapib

EXPERIMENTAL

Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment period.

Drug: Anacetrapib

Placebo

PLACEBO COMPARATOR

Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment period.

Drug: Placebo

Interventions

Anacetrapib DRUG

One oral tablet, orally once daily for 52 weeks

Also known as: MK-0859

Anacetrapib

Placebo DRUG

One oral tablet once daily for 52 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 25743173 BACKGROUND

MeSH Terms

Conditions

Hyperlipoproteinemia Type II

Interventions

anacetrapib

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2012
• First Posted: February 1, 2012
• Study Start: February 3, 2012
• Primary Completion: February 12, 2014
• Study Completion: November 13, 2018
• Last Updated: October 14, 2019
• Results First Posted: August 28, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share