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

Coronary Heart Disease (CHD) Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00685776
• Other study ID #: 0859-019
• Secondary ID: 2007_648
• Status: Completed
• Phase: Phase 3
• First received: May 23, 2008
• Last updated: December 7, 2017
• Start date: March 24, 2008
• Est. completion date: November 23, 2017

Study information

• Verified date: December 2017
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1623
• Est. completion date: November 23, 2017
• Est. primary completion date: July 2, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• CHD Risk-Equivalent Disease
• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease (CHD)
• Heart Diseases
• Myocardial Ischemia

Intervention

Drug:
• anacetrapib
Participants will receive one tablet of anacetrapib 100 mg once daily for 76 weeks.
• Comparator: placebo
Participants will receive one placebo tablet once daily for 76 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in Low Density Lipoprotein Cholesterol		Baseline and 24 weeks
Primary	Number of participants with hepatitis-related adverse experiences		Through 88 weeks
Primary	Number of participants with Alanine Transaminase consecutive elevations greater than or equal to 3xULN (Upper Limit of Normal)		Through 88 weeks
Primary	Number of participants with Aspartate Aminotransferase consecutive elevations greater than or equal to 3xULN		Through 88 weeks
Primary	Number of participants with Creatine Phosphokinase elevations greater than or equal to 10xULN		Through 88 weeks
Primary	Number of participants with Creatine Phosphokinase elevations greater than or equal 10xULN with muscle symptoms		Through 88 weeks
Primary	Number of participants with sodium, chloride, or bicarbonate elevations greater than ULN		Through 88 weeks
Primary	Number of participants with reduction in potassium levels less than LLN (Lower Limit of Normal)		Through 88 weeks
Primary	Number of participants with myalgia		Through 88 weeks
Primary	Number of participants with rhabdomyolysis		Through 88 weeks
Primary	Number of participants with pre-specified adjudicated cardiovascular serious adverse events		Through 88 weeks
Primary	Number of participants with death from any cause		Through 88 weeks
Primary	Number of participants with significant increase in Blood Pressure		Through 88 weeks
Secondary	Change from baseline in High Density Lipoprotein Cholesterol		Baseline, 24 weeks, and 76 weeks
Secondary	Change from baseline in non-High Density Lipoprotein Cholesterol		Baseline, 24 weeks, and 76 weeks
Secondary	Change from baseline in Apolipoprotein B		Baseline, 24 weeks, and 76 weeks
Secondary	Change from baseline in Apolipoprotein A-1		Baseline, 24 weeks, and 76 weeks
Secondary	Change from baseline in Low Density Lipoprotein Cholesterol		Baseline, 24 weeks, and 76 weeks