Study to Assess the Tolerability and Efficacy of Anacetrapib in Patients With Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease (MK-0859-019)

NCT ID: NCT00685776

Last Updated: 2017-12-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1623 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-24
• Study Completion Date: 2017-11-23

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

Conditions

Coronary Heart Disease (CHD); CHD Risk-Equivalent Disease

Keywords

CHD/CHD risk-equivalent disease; Coronary Heart Disease (CHD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Anacetrapib

Participants randomly assigned to anacetrapib in base study will continue same treatment if enrolled in study extension.

Group Type: EXPERIMENTAL

anacetrapib

Intervention Type: DRUG

Participants will receive one tablet of anacetrapib 100 mg once daily for 76 weeks.

Placebo

Participants randomly assigned to placebo in base study will continue same treatment if enrolled in study extension.

Group Type: PLACEBO_COMPARATOR

Comparator: placebo

Intervention Type: DRUG

Participants will receive one placebo tablet once daily for 76 weeks.

Interventions

anacetrapib

Participants will receive one tablet of anacetrapib 100 mg once daily for 76 weeks.

Intervention Type: DRUG

Comparator: placebo

Participants will receive one placebo tablet once daily for 76 weeks.

Intervention Type: DRUG

Other Intervention Names

MK0859

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Countries

Australia; Austria; Canada; Colombia; Finland; France; Germany; Hong Kong; Hungary; Israel; Malaysia; Mexico; Netherlands; New Zealand; Norway; Russia; Spain; Sweden; United States

References

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.

Reference Type: DERIVED

PMID: 25670362 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24737712 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21082868 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 19781408 (View on PubMed)

Other Identifiers

2007_648

Identifier Type: OTHER

Identifier Source: secondary_id

0859-019

Identifier Type: -

Identifier Source: org_study_id