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Trial record 2 of 16 for:    anacetrapib

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01524289
Recruitment Status : Completed
First Posted : February 1, 2012
Results First Posted : August 28, 2019
Last Update Posted : October 14, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Hyperlipoproteinemia Type II
Hypercholesterolemia, Familial
Interventions Drug: Anacetrapib
Drug: Placebo
Enrollment 306
Recruitment Details 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).
Pre-assignment Details The study enrolled participants who were 18 to 80 years old, had a genotype-confirmed or clinical diagnosis of heterozygous familial hypercholesterolemia (HeFH), and had been treated with an optimal dose of statin for at least 6 weeks.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase. Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Period Title: Overall Study
Started 204 102
Treated 203 102
Completed 174 88
Not Completed 30 14
Reason Not Completed
Lost to Follow-up             0             1
Physician Decision             1             0
Protocol Violation             5             1
Withdrawal by Subject             11             7
Adverse Event             12             5
Did not take study medication             1             0
Arm/Group Title Anacetrapib 100 mg Placebo Total
Hide Arm/Group Description Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase. Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase. Total of all reporting groups
Overall Number of Baseline Participants 204 102 306
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 204 participants 102 participants 306 participants
55.0  (11.8) 55.7  (11.9) 55.3  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 204 participants 102 participants 306 participants
Female
84
  41.2%
52
  51.0%
136
  44.4%
Male
120
  58.8%
50
  49.0%
170
  55.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 204 participants 102 participants 306 participants
Asian
2
   1.0%
0
   0.0%
2
   0.7%
Black or African American
0
   0.0%
1
   1.0%
1
   0.3%
Multi-racial
3
   1.5%
1
   1.0%
4
   1.3%
White
199
  97.5%
100
  98.0%
299
  97.7%
1.Primary Outcome
Title Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) - Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) population consisted of all randomized participants who received at least one dose of study treatment, had at least one post randomization observation for the analysis endpoint subsequent to at least one dose of study treatment and had baseline data for those analyses that require baseline data.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 165 85
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent Change
-36.0
(-39.5 to -32.5)
3.7
(-1.2 to 8.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments Between group comparison of percent change from baseline performed using Constrained Longitudinal Data Analysis (cLDA) model.
Method of Estimation Estimation Parameter Difference in Least Squares (LS) Means
Estimated Value -39.7
Confidence Interval (2-Sided) 95%
-45.7 to -33.7
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With Any Adverse Event - Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The all participants as treated (APaT) population consisted of all randomized participants who received at least one dose of study treatment.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 203 102
Measure Type: Number
Unit of Measure: Percentage of Participants
76.4 78.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-11.5 to 8.4
Estimation Comments [Not Specified]
Other Statistical Analysis Miettinen and Nurminen
3.Primary Outcome
Title Percentage of Participants With Any Treatment-Related Adverse Event - Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The APaT population consisted of all randomized participants who received at least one dose of study treatment.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 203 102
Measure Type: Number
Unit of Measure: Percentage of Participants
18.2 13.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 4.5
Confidence Interval (2-Sided) 95%
-4.8 to 12.6
Estimation Comments [Not Specified]
Other Statistical Analysis Miettinen and Nurminen
4.Primary Outcome
Title Percentage of Participants With Any Serious Adverse Event - Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The APaT population consisted of all randomized participants who received at least one dose of study treatment.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 203 102
Measure Type: Number
Unit of Measure: Percentage of Participants
8.9 9.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-8.9 to 5.6
Estimation Comments [Not Specified]
Other Statistical Analysis Miettinen & Nurminen
5.Primary Outcome
Title Percentage of Participants Discontinuing Study Treatment Due to an Adverse Event - Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The APaT population consists of all randomized participants who received at least one dose of study treatment.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 203 102
Measure Type: Number
Unit of Measure: Percentage of Participants
5.9 4.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-5.5 to 6.1
Estimation Comments [Not Specified]
Other Statistical Analysis Miettinen and Nurminen
6.Primary Outcome
Title Percentage of Participants With Changes in Systolic Blood Pressure (SBP) >= 10 mm Hg
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 202 101
Measure Type: Number
Unit of Measure: Percentage of Participants
45.0 53.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-Specified
Statistical Test of Hypothesis P-Value 0.168
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value -8.4
Confidence Interval (2-Sided) 95%
-20.1 to 3.5
Estimation Comments [Not Specified]
7.Primary Outcome
Title Percentage of Participants With Changes in SBP >= 15 mm Hg
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 202 101
Measure Type: Number
Unit of Measure: Percentage of Participants
26.2 33.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Statistical Test of Hypothesis P-Value 0.179
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value -7.4
Confidence Interval (2-Sided) 95%
-18.7 to 3.3
Estimation Comments [Not Specified]
8.Primary Outcome
Title Percentage of Participants With Changes in Diastolic Blood Pressure (DBP) >= 10 mm Hg
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 202 101
Measure Type: Number
Unit of Measure: Percentage of Participants
22.8 36.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value -13.9
Confidence Interval (2-Sided) 95%
-25.0 to -3.1
Estimation Comments [Not Specified]
9.Primary Outcome
Title Percentage of Participants With Sodium Levels > Upper Limit of Normal (ULN)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 202 101
Measure Type: Number
Unit of Measure: Percentage of Participants
11.4 9.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Statistical Test of Hypothesis P-Value 0.696
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
-6.8 to 8.4
Estimation Comments [Not Specified]
10.Primary Outcome
Title Percentage of Participants With Chloride Levels > ULN
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 202 101
Measure Type: Number
Unit of Measure: Percentage of Participants
0.5 0.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Statistical Test of Hypothesis P-Value 0.480
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-3.2 to 2.8
Estimation Comments [Not Specified]
11.Primary Outcome
Title Percentage of Participants With Potassium Levels < Lower Limit of Normal (LLN)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 202 101
Measure Type: Number
Unit of Measure: Percentage of Participants
1.5 1.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Statistical Test of Hypothesis P-Value 0.722
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-4.0 to 3.5
Estimation Comments [Not Specified]
12.Primary Outcome
Title Percentage of Participants With Bicarbonate Levels > ULN
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 202 101
Measure Type: Number
Unit of Measure: Percentage of Participants
0.0 0.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Statistical Test of Hypothesis P-Value >0.999
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-3.7 to 1.9
Estimation Comments [Not Specified]
13.Primary Outcome
Title Percentage of Participants With Consecutive Changes in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x ULN
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 202 101
Measure Type: Number
Unit of Measure: Percentage of Participants
1.5 1.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Statistical Test of Hypothesis P-Value 0.722
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-4.0 to 3.5
Estimation Comments [Not Specified]
14.Primary Outcome
Title Percentage of Participants With Creatine Kinase (CK) Level >=10 x ULN
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 202 101
Measure Type: Number
Unit of Measure: Percentage of Participants
0.0 1.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Statistical Test of Hypothesis P-Value 0.157
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-5.4 to 0.9
Estimation Comments [Not Specified]
15.Primary Outcome
Title Percentage of Participants With CK Level >=10 x ULN With Muscle Spasms
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 202 101
Measure Type: Number
Unit of Measure: Percentage of Participants
0.0 1.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Statistical Test of Hypothesis P-Value 0.157
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-5.4 to 0.9
Estimation Comments [Not Specified]
16.Primary Outcome
Title Percentage of Participants Adjudicated Cardiovascular (CV) SAE
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The APaT population consisted of all randomized participants who received at least one dose of study treatment.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 203 102
Measure Type: Number
Unit of Measure: Percentage of Participants
1.5 0.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Statistical Test of Hypothesis P-Value 0.218
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
-2.2 to 4.3
Estimation Comments [Not Specified]
17.Primary Outcome
Title Percentage of Participants Who Died From Any Cause - Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The APaT population consisted of all randomized participants who received at least one dose of study treatment.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 203 102
Measure Type: Number
Unit of Measure: Percentage of Participants
0.0 0.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Pre-specified
Statistical Test of Hypothesis P-Value >0.999
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-3.6 to 1.9
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Percent Change From Baseline in High-Density Lipoprotein Cholesterol Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population consisted of all randomized participants who received at least one dose of study treatment and had at least one post randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for those analyses that require baseline data.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 173 88
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent Change
105.8
(101.1 to 110.6)
3.7
(-2.8 to 10.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares (LS) Means
Estimated Value 102.1
Confidence Interval (2-Sided) 95%
94.2 to 110.1
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population consisted of all randomized participants who received at least one dose of study treatment and had at least one post randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for those analyses that require baseline data.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 173 88
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent Change
-32.0
(-35.1 to -28.9)
4.4
(0.1 to 8.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -36.4
Confidence Interval (2-Sided) 95%
-41.7 to -31.1
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein (Apo) B Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population consisted of all randomized participants who received at least one dose of study treatment and had at least one post randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for those analyses that require baseline data.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 173 88
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent Change
-19.6
(-22.5 to -16.8)
5.2
(1.3 to 9.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -24.8
Confidence Interval (2-Sided) 95%
-29.5 to -20.1
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein (Apo) A-1 Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population consisted of all randomized participants who received at least one dose of study treatment and had at least one post randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for those analyses that require baseline data.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 173 88
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent Change
35.8
(33.0 to 38.6)
2.9
(-1.0 to 6.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 32.9
Confidence Interval (2-Sided) 95%
28.2 to 37.6
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein(a) (Lp[a]) Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population consisted of all randomized participants who received at least one dose of study treatment and had at least one post randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for those analyses that require baseline data.
Arm/Group Title Anacetrapib 100 mg Placebo
Hide Arm/Group Description:
Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
Overall Number of Participants Analyzed 174 88
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent Change
-31.8
(-37.4 to -26.3)
0.0
(-5.1 to 5.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -27.9
Confidence Interval (2-Sided) 95%
-34.7 to -21.2
Estimation Comments Hodges-Lehmann estimate of the median difference between treatments with a corresponding distribution-free confidence interval (CI) based on Wilcoxon's rank sum test.
Time Frame Up to 64 weeks
Adverse Event Reporting Description Safety population: All participants who received at least 1 dose of study treatment. The treatment phase included AEs reported during the 52-week period from the date of the first dose of study treatment to the last visit on treatment (discontinuation visit or Week 52). The reversal phase included AEs reported during the 12-week period from the day after the treatment phase to the last visit (discontinuation or Week 64).
 
Arm/Group Title Anacetrapib 100 mg - Treatment Phase Placebo - Treatment Phase Anacetrapib 100 mg - Reversal Phase Placebo - Reversal Phase
Hide Arm/Group Description Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks. Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks. Safety data that was reported during the 12-week period from the day after the treatment phase to the participant's last visit (discontinuation visit or week 64). Safety data that was reported during the 12-week period from the day after the treatment phase to the participant's last visit (discontinuation visit or week 64).
All-Cause Mortality
Anacetrapib 100 mg - Treatment Phase Placebo - Treatment Phase Anacetrapib 100 mg - Reversal Phase Placebo - Reversal Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/203 (0.00%)      0/102 (0.00%)      0/196 (0.00%)      0/95 (0.00%)    
Hide Serious Adverse Events
Anacetrapib 100 mg - Treatment Phase Placebo - Treatment Phase Anacetrapib 100 mg - Reversal Phase Placebo - Reversal Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/203 (8.87%)      10/102 (9.80%)      3/196 (1.53%)      2/95 (2.11%)    
Cardiac disorders         
Acute coronary syndrome  1  0/203 (0.00%)  0 0/102 (0.00%)  0 1/196 (0.51%)  1 0/95 (0.00%)  0
Acute myocardial infarction  1  0/203 (0.00%)  0 0/102 (0.00%)  0 1/196 (0.51%)  1 0/95 (0.00%)  0
Angina pectoris  1  4/203 (1.97%)  4 0/102 (0.00%)  0 0/196 (0.00%)  0 1/95 (1.05%)  1
Atrial fibrillation  1  0/203 (0.00%)  0 0/102 (0.00%)  0 0/196 (0.00%)  0 1/95 (1.05%)  1
Angina unstable  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Arteriosclerosis coronary artery  2  0/203 (0.00%)  0 1/102 (0.98%)  1 0/196 (0.00%)  0 0/95 (0.00%)  0
Cardiac arrest  2  0/203 (0.00%)  0 1/102 (0.98%)  1 0/196 (0.00%)  0 0/95 (0.00%)  0
Coronary artery disease  2  1/203 (0.49%)  1 1/102 (0.98%)  1 0/196 (0.00%)  0 0/95 (0.00%)  0
Ischaemic cardiomyopathy  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Myocardial ischaemia  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Ventricular fibrillation  2  0/203 (0.00%)  0 1/102 (0.98%)  1 0/196 (0.00%)  0 0/95 (0.00%)  0
Gastrointestinal disorders         
Pancreatitis  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
General disorders         
Device malfunction  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Drug resistance  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Medical device discomfort  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Hepatobiliary disorders         
Cholelithiasis  1  1/203 (0.49%)  1 0/102 (0.00%)  0 1/196 (0.51%)  1 0/95 (0.00%)  0
Infections and infestations         
Endocarditis  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Intervertebral discitis  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Pyelonephritis  2  0/203 (0.00%)  0 1/102 (0.98%)  1 0/196 (0.00%)  0 0/95 (0.00%)  0
Staphylococcal bacteraemia  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Injury, poisoning and procedural complications         
Thoracic vertebral fracture  1  0/203 (0.00%)  0 0/102 (0.00%)  0 1/196 (0.51%)  1 0/95 (0.00%)  0
Gastrointestinal anastomotic leak  2  0/203 (0.00%)  0 1/102 (0.98%)  1 0/196 (0.00%)  0 0/95 (0.00%)  0
Post procedural haemorrhage  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Metabolism and nutrition disorders         
Type 2 diabetes mellitus  2  0/203 (0.00%)  0 1/102 (0.98%)  1 0/196 (0.00%)  0 0/95 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Basal cell carcinoma  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Breast cancer  2  1/203 (0.49%)  1 1/102 (0.98%)  1 0/196 (0.00%)  0 0/95 (0.00%)  0
Colon cancer  2  0/203 (0.00%)  0 1/102 (0.98%)  1 0/196 (0.00%)  0 0/95 (0.00%)  0
Prostate cancer  2  0/203 (0.00%)  0 1/102 (0.98%)  1 0/196 (0.00%)  0 0/95 (0.00%)  0
Nervous system disorders         
Migraine with aura  1  0/203 (0.00%)  0 0/102 (0.00%)  0 0/196 (0.00%)  0 1/95 (1.05%)  1
Transient ischaemic attack  1  0/203 (0.00%)  0 0/102 (0.00%)  0 0/196 (0.00%)  0 1/95 (1.05%)  1
Loss of consciousness  2  0/203 (0.00%)  0 1/102 (0.98%)  1 0/196 (0.00%)  0 0/95 (0.00%)  0
Psychiatric disorders         
Emotional distress  2  0/203 (0.00%)  0 1/102 (0.98%)  1 0/196 (0.00%)  0 0/95 (0.00%)  0
Renal and urinary disorders         
Renal colic  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Reproductive system and breast disorders         
Uterovaginal prolapse  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Asthma  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
Pleurisy  2  1/203 (0.49%)  1 0/102 (0.00%)  0 0/196 (0.00%)  0 0/95 (0.00%)  0
1
Term from vocabulary, 16.1
2
Term from vocabulary, MedDRA version 16.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Anacetrapib 100 mg - Treatment Phase Placebo - Treatment Phase Anacetrapib 100 mg - Reversal Phase Placebo - Reversal Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   87/203 (42.86%)      41/102 (40.20%)      0/196 (0.00%)      0/95 (0.00%)    
Gastrointestinal disorders         
Diarrhoea  1  16/203 (7.88%)  19 9/102 (8.82%)  10 0/196 (0.00%)  0 0/95 (0.00%)  0
Infections and infestations         
Gastroenteritis  1  2/203 (0.99%)  2 6/102 (5.88%)  7 0/196 (0.00%)  0 0/95 (0.00%)  0
Influenza  1  20/203 (9.85%)  22 11/102 (10.78%)  11 0/196 (0.00%)  0 0/95 (0.00%)  0
Nasopharyngitis  1  40/203 (19.70%)  50 19/102 (18.63%)  21 0/196 (0.00%)  0 0/95 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Arthralgia  1  12/203 (5.91%)  15 2/102 (1.96%)  2 0/196 (0.00%)  0 0/95 (0.00%)  0
Myalgia  1  18/203 (8.87%)  26 4/102 (3.92%)  5 0/196 (0.00%)  0 0/95 (0.00%)  0
Nervous system disorders         
Headache  1  16/203 (7.88%)  19 6/102 (5.88%)  7 0/196 (0.00%)  0 0/95 (0.00%)  0
1
Term from vocabulary, MedDRA version 16.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication timelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01524289    
Other Study ID Numbers: 0859-020
2011-004525-27 ( EudraCT Number )
MK-0859-020 ( Other Identifier: Merck )
First Submitted: January 30, 2012
First Posted: February 1, 2012
Results First Submitted: August 5, 2019
Results First Posted: August 28, 2019
Last Update Posted: October 14, 2019