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Completed

NCT Number: NCT00685776

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

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.

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Key information

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Anacetrapib

Drug

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

Other names: MK0859

Comparator: placebo

Drug

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

Primary outcomes

  1. Change from baseline in Low Density Lipoprotein Cholesterol

    Time frame: Baseline and 24 weeks

  2. Number of participants with hepatitis-related adverse experiences

    Time frame: Through 88 weeks

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

    Time frame: Through 88 weeks

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

    Time frame: Through 88 weeks

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

    Time frame: Through 88 weeks

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

    Time frame: Through 88 weeks

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

    Time frame: Through 88 weeks

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

    Time frame: Through 88 weeks

  9. Number of participants with myalgia

    Time frame: Through 88 weeks

  10. Number of participants with rhabdomyolysis

    Time frame: Through 88 weeks

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

    Time frame: Through 88 weeks

  12. Number of participants with death from any cause

    Time frame: Through 88 weeks

  13. Number of participants with significant increase in Blood Pressure

    Time frame: Through 88 weeks

Secondary outcomes

  1. Change from baseline in High Density Lipoprotein Cholesterol

    Time frame: Baseline, 24 weeks, and 76 weeks

  2. Change from baseline in non-High Density Lipoprotein Cholesterol

    Time frame: Baseline, 24 weeks, and 76 weeks

  3. Change from baseline in Apolipoprotein B

    Time frame: Baseline, 24 weeks, and 76 weeks

  4. Change from baseline in Apolipoprotein A-1

    Time frame: Baseline, 24 weeks, and 76 weeks

  5. Change from baseline in Low Density Lipoprotein Cholesterol

    Time frame: Baseline, 24 weeks, and 76 weeks

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study 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

Acronym: DEFINE

Important dates

Study start
2008
Primary completion
2009
Study completion
2017
First posted
May 28, 2008
Registry last updated
Dec 11, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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