CClinicalTrials.gg
Sign In
CompletedNCT01524289REALIZEUpdated Oct 14, 2019Results posted

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

A Phase 3 interventional study of Anacetrapib and Placebo in Hyperlipoproteinemia Type II and Hypercholesterolemia, Familial, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2019-10-14.

Sponsored by Merck Sharp & Dohme LLC · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
306
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study 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).

02

Conditions studied

  • Hyperlipoproteinemia Type II
  • Hypercholesterolemia, Familial
03

In context

Hyperlipoproteinemia Type II

245 studies on the registry are indexed under Hyperlipoproteinemia Type II; 52 are open to participants now.

This study's enrollment of 306 is above the median of 86 across 170 interventional studies indexed under Hyperlipoproteinemia Type II.

Browse Hyperlipoproteinemia Type II studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
306 participants (actual)

Study arms

  • Experimental
    Anacetrapib

    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 comparator
    Placebo

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

    Drug: Placebo

Interventions

  • DrugAnacetrapib

    One oral tablet, orally once daily for 52 weeks

    Also known as: MK-0859

  • DrugPlacebo

    One oral tablet once daily for 52 weeks

06

What researchers measure

Primary outcomes

  1. 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 \[Week 52\]).

    Time frame: Baseline and Week 52

  2. 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.

    Time frame: Up to 52 weeks

  3. 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.

    Time frame: Up to 52 weeks

  4. 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.

    Time frame: Up to 52 weeks

  5. 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.

    Time frame: Up to 52 weeks

  6. 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.

    Time frame: Up to 52 weeks

  7. 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.

    Time frame: Up to 52 weeks

  8. 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.

    Time frame: Up to 52 weeks

  9. 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.

    Time frame: Up to 52 weeks

  10. 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.

    Time frame: Up to 52 weeks

  11. 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.

    Time frame: Up to 52 weeks

  12. 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.

    Time frame: Up to 52 weeks

  13. 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.

    Time frame: Up to 52 weeks

  14. 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.

    Time frame: Up to 52 weeks

  15. 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.

    Time frame: Up to 52 weeks

  16. 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.

    Time frame: Up to 52 weeks

  17. 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.

    Time frame: Up to 52 weeks

Secondary outcomes

  1. Percent Change From Baseline in High-Density Lipoprotein Cholesterol Levels

    The efficacy of adding anacetrapib 100 mg relative to placebo on plasma concentrations of high-density lipoprotein cholesterol (HDL-C) was evaluated at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation.

    Time frame: Baseline and Week 52

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

    The efficacy of adding anacetrapib 100 mg was evaluated relative to placebo on plasma concentrations of non-high-density lipoprotein cholesterol (HDL-C) for the FAS population at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation.

    Time frame: Baseline and Week 52

  3. Percent Change From Baseline in Apolipoprotein (Apo) B Levels

    The efficacy of adding anacetrapib 100 mg was evaluated relative to placebo on plasma concentrations of apolipoprotein (Apo) B for the FAS population at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation.

    Time frame: Baseline and Week 52

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

    The efficacy of adding anacetrapib 100 mg was evaluated relative to placebo on plasma concentrations of Apo A-1 for the FAS population at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation.

    Time frame: Baseline and Week 52

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

    The efficacy of adding anacetrapib 100 mg was evaluated relative to placebo on plasma concentrations of lipoprotein(a) (Lp\[a\]) for the FAS population at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation.

    Time frame: Baseline and Week 52

07

Results

Posted Aug 28, 2019

Participant flow

This study was conducted at 26 study centers. Participants were to complete a 2-week placebo run-in period, a 52-week randomized treatment phase and a 12-week reversal phase (safety follow-up).

Participant flow — Overall Study
MilestoneAnacetrapib 100 mgPlacebo
Started204102
Treated203102
Completed17488
Not completed3014
Withdrew: Lost to follow-up01
Withdrew: Physician decision10
Withdrew: Protocol violation51
Withdrew: Withdrawal by subject117
Withdrew: Adverse event125
Withdrew: Did not take study medication10

Outcome measures

PrimaryPercent 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 \[Week 52\]).

Time frame:
Baseline and Week 52
Reported as:
Least squares mean · Percent Change
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) - Treatment Phase
Percent ChangeAnacetrapib 100 mgPlacebo
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) - Treatment Phase-36.0 (-39.5 to -32.5)3.7 (-1.2 to 8.6)
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Constrained Longitudinal Data Analysis · p = <0.001 · Difference in least squares (ls) means: -39.7 · 95% CI -45.7 to -33.7Between group comparison of percent change from baseline performed using Constrained Longitudinal Data Analysis (cLDA) model.
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Any Adverse Event - Treatment Phase
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants With Any Adverse Event - Treatment Phase76.478.4
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Difference in percentages: -2.1 · 95% CI -11.5 to 8.4
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Any Treatment-Related Adverse Event - Treatment Phase
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants With Any Treatment-Related Adverse Event - Treatment Phase18.213.7
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Difference in percentages: 4.5 · 95% CI -4.8 to 12.6
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Any Serious Adverse Event - Treatment Phase
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants With Any Serious Adverse Event - Treatment Phase8.99.8
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Difference in percentages: -0.9 · 95% CI -8.9 to 5.6
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants Discontinuing Study Treatment Due to an Adverse Event - Treatment Phase
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants Discontinuing Study Treatment Due to an Adverse Event - Treatment Phase5.94.9
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Difference in percentages: 1.0 · 95% CI -5.5 to 6.1
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Changes in Systolic Blood Pressure (SBP) >= 10 mm Hg
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants With Changes in Systolic Blood Pressure (SBP) >= 10 mm Hg45.053.5
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Miettinen and Nurminen · p = 0.168 · Difference in percentages: -8.4 · 95% CI -20.1 to 3.5
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Changes in SBP >= 15 mm Hg
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants With Changes in SBP >= 15 mm Hg26.233.7
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Miettinen and Nurminen · p = 0.179 · Difference in percentages: -7.4 · 95% CI -18.7 to 3.3
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Changes in Diastolic Blood Pressure (DBP) >= 10 mm Hg
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants With Changes in Diastolic Blood Pressure (DBP) >= 10 mm Hg22.836.6
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Miettinen and Nurminen · p = 0.011 · Difference in percentages: -13.9 · 95% CI -25.0 to -3.1
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Sodium Levels > Upper Limit of Normal (ULN)
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants With Sodium Levels > Upper Limit of Normal (ULN)11.49.9
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Miettinen and Nurminen · p = 0.696 · Difference in percentages: 1.5 · 95% CI -6.8 to 8.4
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Chloride Levels > ULN
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants With Chloride Levels > ULN0.50.0
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Miettinen and Nurminen · p = 0.480 · Difference in percentages: 0.5 · 95% CI -3.2 to 2.8
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Potassium Levels < Lower Limit of Normal (LLN)
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants With Potassium Levels < Lower Limit of Normal (LLN)1.51.0
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Miettinen and Nurminen · p = 0.722 · Difference in percentages: 0.5 · 95% CI -4.0 to 3.5
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Bicarbonate Levels > ULN
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants With Bicarbonate Levels > ULN0.00.0
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Miettinen and Nurminen · p = >0.999 · Difference in percentages: 0.0 · 95% CI -3.7 to 1.9
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Consecutive Changes in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x ULN
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants With Consecutive Changes in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x ULN1.51.0
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Miettinen and Nurminen · p = 0.722 · Difference in percentages: 0.5 · 95% CI -4.0 to 3.5
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Creatine Kinase (CK) Level >=10 x ULN
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants With Creatine Kinase (CK) Level >=10 x ULN0.01.0
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Miettinen and Nurminen · p = 0.157 · Difference in percentages: -1.0 · 95% CI -5.4 to 0.9
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With CK Level >=10 x ULN With Muscle Spasms
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants With CK Level >=10 x ULN With Muscle Spasms0.01.0
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Miettinen and Nurminen · p = 0.157 · Difference in percentages: -1.0 · 95% CI -5.4 to 0.9
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants Adjudicated Cardiovascular (CV) SAE
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants Adjudicated Cardiovascular (CV) SAE1.50.0
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Miettinen and Nurminen · p = 0.218 · Difference in percentages: 1.5 · 95% CI -2.2 to 4.3
PrimaryPercentage 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.

Time frame:
Up to 52 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants Who Died From Any Cause - Treatment Phase
Percentage of ParticipantsAnacetrapib 100 mgPlacebo
Percentage of Participants Who Died From Any Cause - Treatment Phase0.00.0
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Miettinen and Nurminen · p = >0.999 · Difference in percentages: 0.0 · 95% CI -3.6 to 1.9
SecondaryPercent Change From Baseline in High-Density Lipoprotein Cholesterol Levels

The efficacy of adding anacetrapib 100 mg relative to placebo on plasma concentrations of high-density lipoprotein cholesterol (HDL-C) was evaluated at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation.

Time frame:
Baseline and Week 52
Reported as:
Least squares mean · Percent Change
Percent Change From Baseline in High-Density Lipoprotein Cholesterol Levels
Percent ChangeAnacetrapib 100 mgPlacebo
Percent Change From Baseline in High-Density Lipoprotein Cholesterol Levels105.8 (101.1 to 110.6)3.7 (-2.8 to 10.3)
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Constrained Longitudinal Data Analysis · p = <0.001 · Difference in least squares (ls) means: 102.1 · 95% CI 94.2 to 110.1
SecondaryPercent Change From Baseline in Non-High-Density Lipoprotein Cholesterol Levels

The efficacy of adding anacetrapib 100 mg was evaluated relative to placebo on plasma concentrations of non-high-density lipoprotein cholesterol (HDL-C) for the FAS population at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation.

Time frame:
Baseline and Week 52
Reported as:
Least squares mean · Percent Change
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol Levels
Percent ChangeAnacetrapib 100 mgPlacebo
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol Levels-32.0 (-35.1 to -28.9)4.4 (0.1 to 8.8)
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Constrained Longitudinal Data Analysis · p = <0.001 · Difference in ls means: -36.4 · 95% CI -41.7 to -31.1
SecondaryPercent Change From Baseline in Apolipoprotein (Apo) B Levels

The efficacy of adding anacetrapib 100 mg was evaluated relative to placebo on plasma concentrations of apolipoprotein (Apo) B for the FAS population at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation.

Time frame:
Baseline and Week 52
Reported as:
Number · Percent Change
Percent Change From Baseline in Apolipoprotein (Apo) B Levels
Percent ChangeAnacetrapib 100 mgPlacebo
Percent Change From Baseline in Apolipoprotein (Apo) B Levels-19.6 (-22.5 to -16.8)5.2 (1.3 to 9.1)
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Constrained Longitudinal Data Analysis · p = <0.001 · Difference in ls means: -24.8 · 95% CI -29.5 to -20.1
SecondaryPercent Change From Baseline in Apolipoprotein (Apo) A-1 Levels

The efficacy of adding anacetrapib 100 mg was evaluated relative to placebo on plasma concentrations of Apo A-1 for the FAS population at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation.

Time frame:
Baseline and Week 52
Reported as:
Number · Percent Change
Percent Change From Baseline in Apolipoprotein (Apo) A-1 Levels
Percent ChangeAnacetrapib 100 mgPlacebo
Percent Change From Baseline in Apolipoprotein (Apo) A-1 Levels35.8 (33.0 to 38.6)2.9 (-1.0 to 6.8)
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Constrained Longitudinal Data Analysis · p = <0.001 · Difference in ls means: 32.9 · 95% CI 28.2 to 37.6
SecondaryPercent Change From Baseline in Lipoprotein(a) (Lp[a]) Levels

The efficacy of adding anacetrapib 100 mg was evaluated relative to placebo on plasma concentrations of lipoprotein(a) (Lp\[a\]) for the FAS population at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation.

Time frame:
Baseline and Week 52
Reported as:
Number · Percent Change
Percent Change From Baseline in Lipoprotein(a) (Lp[a]) Levels
Percent ChangeAnacetrapib 100 mgPlacebo
Percent Change From Baseline in Lipoprotein(a) (Lp[a]) Levels-31.8 (-37.4 to -26.3)0.0 (-5.1 to 5.1)
Statistical analysis
  • Anacetrapib 100 mg vs Placebo · Wilcoxon (Mann-Whitney) · p = <0.001 · Median difference (final values): -27.9 · 95% CI -34.7 to -21.2Hodges-Lehmann estimate of the median difference between treatments with a corresponding distribution-free confidence interval (CI) based on Wilcoxon's rank sum test.

Adverse events

Collected over Up to 64 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Anacetrapib 100 mg - Treatment Phase0/203 (0%)18/203 (8.9%)87/203 (42.9%)
Placebo - Treatment Phase0/102 (0%)10/102 (9.8%)41/102 (40.2%)
Anacetrapib 100 mg - Reversal Phase0/196 (0%)3/196 (1.5%)0/196 (0%)
Placebo - Reversal Phase0/95 (0%)2/95 (2.1%)0/95 (0%)
Most frequent serious events
Showing 10 of 36
Most frequent serious events
EventAnacetrapib 100 mg - Treatment PhasePlacebo - Treatment PhaseAnacetrapib 100 mg - Reversal PhasePlacebo - Reversal Phase
Angina pectorisCardiac disorders4/2030/1020/1961/95
Atrial fibrillationCardiac disorders0/2030/1020/1961/95
Migraine with auraNervous system disorders0/2030/1020/1961/95
Transient ischaemic attackNervous system disorders0/2030/1020/1961/95
Arteriosclerosis coronary arteryCardiac disorders0/2031/1020/1960/95
Cardiac arrestCardiac disorders0/2031/1020/1960/95
Coronary artery diseaseCardiac disorders1/2031/1020/1960/95
Ventricular fibrillationCardiac disorders0/2031/1020/1960/95
PyelonephritisInfections and infestations0/2031/1020/1960/95
Gastrointestinal anastomotic leakInjury, poisoning and procedural complications0/2031/1020/1960/95
Most frequent other events
Most frequent other events
EventAnacetrapib 100 mg - Treatment PhasePlacebo - Treatment PhaseAnacetrapib 100 mg - Reversal PhasePlacebo - Reversal Phase
NasopharyngitisInfections and infestations40/20319/1020/1960/95
InfluenzaInfections and infestations20/20311/1020/1960/95
MyalgiaMusculoskeletal and connective tissue disorders18/2034/1020/1960/95
DiarrhoeaGastrointestinal disorders16/2039/1020/1960/95
HeadacheNervous system disorders16/2036/1020/1960/95
ArthralgiaMusculoskeletal and connective tissue disorders12/2032/1020/1960/95
GastroenteritisInfections and infestations2/2036/1020/1960/95

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Anacetrapib 100 mgPlaceboTotal
Mean55.0 ± 11.855.7 ± 11.955.3 ± 11.8
Sex: Female, Male
Sex: Female, Male(Participants)Anacetrapib 100 mgPlaceboTotal
Female8452136
Male12050170
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Anacetrapib 100 mgPlaceboTotal
Asian202
Black or African American011
Multi-racial314
White199100299
08

Study locations

No study locations are listed for this record.

09

References and documents

Publications

  • 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. PubMed 25743173 ↗

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 14, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01524289
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Feb 1, 2012
Start date
Feb 3, 2012
Primary completion
Feb 12, 2014
Completion
Nov 13, 2018
Results posted
Aug 28, 2019
Last update
Oct 14, 2019

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2019. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Hyperlipoproteinemia Type II→

Other studies from this sponsor

Merck Sharp & Dohme LLC

Start the discussion