Study to Assess the Tolerability and Efficacy of Anacetrapib in Patients With Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease (MK-0859-019) (DEFINE)
Primary Purpose
Coronary Heart Disease (CHD), CHD Risk-Equivalent Disease
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
anacetrapib
Comparator: placebo
Sponsored by
About this trial
This is an interventional treatment trial for Coronary Heart Disease (CHD) focused on measuring CHD/CHD risk-equivalent disease, Coronary Heart Disease (CHD)
Eligibility Criteria
Inclusion Criteria:
Base Study:
- Patient has Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease and is treated with a statin, with well controlled LDL-C
Extension Study:
- Patient has completed the base study including the reversibility period (i.e. 12 or to up to 24 weeks).
- Patient is on statin therapy ± lipid-modifying therapy since the end of the base study and planning to continue taking a statin throughout the study
Exclusion Criteria:
- History of heart failure, arrhythmias, heart attack, unstable angina, or stroke within 3 months prior to screening, uncontrolled blood pressure, uncontrolled high cholesterol or liver disease.
- History of mental instability, drug/alcohol abuse within the past 5 years
- Pregnant or breast-feeding
- History of cancer within the last 5 years
- HIV positive
- Donated blood products within 8 weeks
- Currently participating or have participated in a study with an investigational compound within the last 30 days
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Anacetrapib
Placebo
Arm Description
Participants randomly assigned to anacetrapib in base study will continue same treatment if enrolled in study extension.
Participants randomly assigned to placebo in base study will continue same treatment if enrolled in study extension.
Outcomes
Primary Outcome Measures
Change from baseline in Low Density Lipoprotein Cholesterol
Number of participants with hepatitis-related adverse experiences
Number of participants with Alanine Transaminase consecutive elevations greater than or equal to 3xULN (Upper Limit of Normal)
Number of participants with Aspartate Aminotransferase consecutive elevations greater than or equal to 3xULN
Number of participants with Creatine Phosphokinase elevations greater than or equal to 10xULN
Number of participants with Creatine Phosphokinase elevations greater than or equal 10xULN with muscle symptoms
Number of participants with sodium, chloride, or bicarbonate elevations greater than ULN
Number of participants with reduction in potassium levels less than LLN (Lower Limit of Normal)
Number of participants with myalgia
Number of participants with rhabdomyolysis
Number of participants with pre-specified adjudicated cardiovascular serious adverse events
Number of participants with death from any cause
Number of participants with significant increase in Blood Pressure
Secondary Outcome Measures
Change from baseline in High Density Lipoprotein Cholesterol
Change from baseline in non-High Density Lipoprotein Cholesterol
Change from baseline in Apolipoprotein B
Change from baseline in Apolipoprotein A-1
Change from baseline in Low Density Lipoprotein Cholesterol
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00685776
Brief Title
Study to Assess the Tolerability and Efficacy of Anacetrapib in Patients With Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease (MK-0859-019)
Acronym
DEFINE
Official Title
A 76-Week, Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Assess the Tolerability and Efficacy of Anacetrapib When Added to Ongoing Therapy With a Statin in Patients With Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
March 24, 2008 (Actual)
Primary Completion Date
July 2, 2009 (Actual)
Study Completion Date
November 23, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will evaluate the efficacy of anacetrapib (100 mg) for 24 weeks relative to placebo, on plasma concentrations of Low Density Lipoprotein Cholesterol and assess the safety and tolerability of anacetrapib (100 mg) in participants with CHD/CHD risk-equivalent disease on stable dose regimen of statin with or without other lipid-modifying therapy. The two year extension to this study will further evaluate the long-term safety profile and efficacy of anacetrapib in CHD/CHD-risk equivalent patients who are on ongoing therapy with a statin with or without other lipid-modifying therapy.
Detailed Description
The 76 week treatment period is followed by a 12 week reversibility phase which can be extended by up to another 12 weeks in order to allow participants who have completed their week 88 visit to continue in the study until the Extension study is ready to be implemented.
In the optional extension, participants will be assigned to the same treatment arm to which they were assigned in the base study. The total duration of the extension study will be up to 116 weeks; which will include a 2 year treatment period, followed by a 12 week reversal phase. A post-extension study follow-up phone call will be completed 12 weeks after discontinuation or completion of study treatment. Participants previously treated with anacetrapib or placebo will be invited in a 4:1 ratio in an optional extended reversal phase. The total duration of the extended reversal phase will be 1 year.
Participants previously treated with anacetrapib in the DEFINE study will be followed periodically for up to 4 years to determine plasma levels of anacetrapib. Participants will also be invited to participate in a sub-study consisting of one clinic visit to measure anacetrapib levels in the plasma and the subcutaneous adipose tissue.
ACRONYM: DEFINE= Determining the EFficacy and Tolerability of Cholesteryl ester transfer protein (CETP) INhibition with AnacEtrapib
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Heart Disease (CHD), CHD Risk-Equivalent Disease
Keywords
CHD/CHD risk-equivalent disease, Coronary Heart Disease (CHD)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
1623 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Anacetrapib
Arm Type
Experimental
Arm Description
Participants randomly assigned to anacetrapib in base study will continue same treatment if enrolled in study extension.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants randomly assigned to placebo in base study will continue same treatment if enrolled in study extension.
Intervention Type
Drug
Intervention Name(s)
anacetrapib
Other Intervention Name(s)
MK0859
Intervention Description
Participants will receive one tablet of anacetrapib 100 mg once daily for 76 weeks.
Intervention Type
Drug
Intervention Name(s)
Comparator: placebo
Intervention Description
Participants will receive one placebo tablet once daily for 76 weeks.
Primary Outcome Measure Information:
Title
Change from baseline in Low Density Lipoprotein Cholesterol
Time Frame
Baseline and 24 weeks
Title
Number of participants with hepatitis-related adverse experiences
Time Frame
Through 88 weeks
Title
Number of participants with Alanine Transaminase consecutive elevations greater than or equal to 3xULN (Upper Limit of Normal)
Time Frame
Through 88 weeks
Title
Number of participants with Aspartate Aminotransferase consecutive elevations greater than or equal to 3xULN
Time Frame
Through 88 weeks
Title
Number of participants with Creatine Phosphokinase elevations greater than or equal to 10xULN
Time Frame
Through 88 weeks
Title
Number of participants with Creatine Phosphokinase elevations greater than or equal 10xULN with muscle symptoms
Time Frame
Through 88 weeks
Title
Number of participants with sodium, chloride, or bicarbonate elevations greater than ULN
Time Frame
Through 88 weeks
Title
Number of participants with reduction in potassium levels less than LLN (Lower Limit of Normal)
Time Frame
Through 88 weeks
Title
Number of participants with myalgia
Time Frame
Through 88 weeks
Title
Number of participants with rhabdomyolysis
Time Frame
Through 88 weeks
Title
Number of participants with pre-specified adjudicated cardiovascular serious adverse events
Time Frame
Through 88 weeks
Title
Number of participants with death from any cause
Time Frame
Through 88 weeks
Title
Number of participants with significant increase in Blood Pressure
Time Frame
Through 88 weeks
Secondary Outcome Measure Information:
Title
Change from baseline in High Density Lipoprotein Cholesterol
Time Frame
Baseline, 24 weeks, and 76 weeks
Title
Change from baseline in non-High Density Lipoprotein Cholesterol
Time Frame
Baseline, 24 weeks, and 76 weeks
Title
Change from baseline in Apolipoprotein B
Time Frame
Baseline, 24 weeks, and 76 weeks
Title
Change from baseline in Apolipoprotein A-1
Time Frame
Baseline, 24 weeks, and 76 weeks
Title
Change from baseline in Low Density Lipoprotein Cholesterol
Time Frame
Baseline, 24 weeks, and 76 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Base Study:
Patient has Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease and is treated with a statin, with well controlled LDL-C
Extension Study:
Patient has completed the base study including the reversibility period (i.e. 12 or to up to 24 weeks).
Patient is on statin therapy ± lipid-modifying therapy since the end of the base study and planning to continue taking a statin throughout the study
Exclusion Criteria:
History of heart failure, arrhythmias, heart attack, unstable angina, or stroke within 3 months prior to screening, uncontrolled blood pressure, uncontrolled high cholesterol or liver disease.
History of mental instability, drug/alcohol abuse within the past 5 years
Pregnant or breast-feeding
History of cancer within the last 5 years
HIV positive
Donated blood products within 8 weeks
Currently participating or have participated in a study with an investigational compound within the last 30 days
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
25670362
Citation
Brinton EA, Kher U, Shah S, Cannon CP, Davidson M, Gotto AM, Ashraf TB, McCrary Sisk C, Dansky H, Mitchel Y, Barter P; DEFINE Investigators. Effects of anacetrapib on plasma lipids in specific patient subgroups in the DEFINE (Determining the Efficacy and Tolerability of CETP INhibition with AnacEtrapib) trial. J Clin Lipidol. 2015 Jan-Feb;9(1):65-71. doi: 10.1016/j.jacl.2014.10.005. Epub 2014 Nov 4.
Results Reference
derived
PubMed Identifier
24737712
Citation
Gotto AM Jr, Kher U, Chatterjee MS, Liu Y, Li XS, Vaidya S, Cannon CP, Brinton EA, Moon JE, Shah S, Dansky HM, Mitchel Y, Barter P; DEFINE Investigators. Lipids, safety parameters, and drug concentrations after an additional 2 years of treatment with anacetrapib in the DEFINE study. J Cardiovasc Pharmacol Ther. 2014 Nov;19(6):543-9. doi: 10.1177/1074248414529621. Epub 2014 Apr 14.
Results Reference
derived
PubMed Identifier
21082868
Citation
Cannon CP, Shah S, Dansky HM, Davidson M, Brinton EA, Gotto AM, Stepanavage M, Liu SX, Gibbons P, Ashraf TB, Zafarino J, Mitchel Y, Barter P; Determining the Efficacy and Tolerability Investigators. Safety of anacetrapib in patients with or at high risk for coronary heart disease. N Engl J Med. 2010 Dec 16;363(25):2406-15. doi: 10.1056/NEJMoa1009744. Epub 2010 Nov 17.
Results Reference
derived
PubMed Identifier
19781408
Citation
Cannon CP, Dansky HM, Davidson M, Gotto AM Jr, Brinton EA, Gould AL, Stepanavage M, Liu SX, Shah S, Rubino J, Gibbons P, Hermanowski-Vosatka A, Binkowitz B, Mitchel Y, Barter P; DEFINE investigators. Design of the DEFINE trial: determining the EFficacy and tolerability of CETP INhibition with AnacEtrapib. Am Heart J. 2009 Oct;158(4):513-519.e3. doi: 10.1016/j.ahj.2009.07.028.
Results Reference
derived
Learn more about this trial
Study to Assess the Tolerability and Efficacy of Anacetrapib in Patients With Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease (MK-0859-019)
We'll reach out to this number within 24 hrs