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

NCT00685776 | Completed Phase 3 DMC

• 2 other identifiers: 0859-0192007_648
• Study Type: interventional
• Target: 1,623
• Locations: 0 countries
• Sites: N/A

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (13)

• Change from baseline in Low Density Lipoprotein Cholesterol

  Baseline and 24 weeks

• Number of participants with hepatitis-related adverse experiences

  Through 88 weeks

• Number of participants with Alanine Transaminase consecutive elevations greater than or equal to 3xULN (Upper Limit of Normal)

  Through 88 weeks

• Number of participants with Aspartate Aminotransferase consecutive elevations greater than or equal to 3xULN

  Through 88 weeks

• Number of participants with Creatine Phosphokinase elevations greater than or equal to 10xULN

  Through 88 weeks

• Number of participants with Creatine Phosphokinase elevations greater than or equal 10xULN with muscle symptoms

  Through 88 weeks

• Number of participants with sodium, chloride, or bicarbonate elevations greater than ULN

  Through 88 weeks

• Number of participants with reduction in potassium levels less than LLN (Lower Limit of Normal)

  Through 88 weeks

• Number of participants with myalgia

  Through 88 weeks

• Number of participants with rhabdomyolysis

  Through 88 weeks

• Number of participants with pre-specified adjudicated cardiovascular serious adverse events

  Through 88 weeks

• Number of participants with death from any cause

  Through 88 weeks

• Number of participants with significant increase in Blood Pressure

  Through 88 weeks

Secondary Outcomes (5)

• Change from baseline in High Density Lipoprotein Cholesterol

  Baseline, 24 weeks, and 76 weeks

• Change from baseline in non-High Density Lipoprotein Cholesterol

  Baseline, 24 weeks, and 76 weeks

• Change from baseline in Apolipoprotein B

  Baseline, 24 weeks, and 76 weeks

• Change from baseline in Apolipoprotein A-1

  Baseline, 24 weeks, and 76 weeks

• Change from baseline in Low Density Lipoprotein Cholesterol

  Baseline, 24 weeks, and 76 weeks

Study Arms (2)

Anacetrapib

EXPERIMENTAL

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

Drug: anacetrapib

Placebo

PLACEBO COMPARATOR

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

Drug: Comparator: placebo

Interventions

anacetrapib DRUG

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

Also known as: MK0859

Anacetrapib

Comparator: placebo DRUG

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

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (4)

• 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.

  PMID: 25670362 DERIVED

• 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.

  PMID: 24737712 DERIVED

• 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.

  PMID: 21082868 DERIVED

• 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.

  PMID: 19781408 DERIVED

MeSH Terms

Conditions

Coronary Disease

Interventions

anacetrapib

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 23, 2008
• First Posted: May 28, 2008
• Study Start: March 24, 2008
• Primary Completion: July 2, 2009
• Study Completion: November 23, 2017
• Last Updated: December 11, 2017

Record last verified: 2017-12