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)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00685776
First received: May 23, 2008
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Coronary Heart Disease (CHD)
CHD Risk-Equivalent Disease
Drug: anacetrapib
Drug: Comparator: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change from baseline in Low Density Lipoprotein Cholesterol [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  • Number of participants with hepatitis-related adverse experiences [ Time Frame: Through 88 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants with Alanine Transaminase consecutive elevations greater than or equal to 3xULN (Upper Limit of Normal) [ Time Frame: Through 88 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants with Aspartate Aminotransferase consecutive elevations greater than or equal to 3xULN [ Time Frame: Through 88 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants with Creatine Phosphokinase elevations greater than or equal to 10xULN [ Time Frame: Through 88 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants with Creatine Phosphokinase elevations greater than or equal 10xULN with muscle symptoms [ Time Frame: Through 88 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants with sodium, chloride, or bicarbonate elevations greater than ULN [ Time Frame: Through 88 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants with reduction in potassium levels less than LLN (Lower Limit of Normal) [ Time Frame: Through 88 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants with myalgia [ Time Frame: Through 88 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants with rhabdomyolysis [ Time Frame: Through 88 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants with pre-specified adjudicated cardiovascular serious adverse events [ Time Frame: Through 88 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants with death from any cause [ Time Frame: Through 88 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants with significant increase in Blood Pressure [ Time Frame: Through 88 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from baseline in High Density Lipoprotein Cholesterol [ Time Frame: Baseline, 24 weeks, and 76 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in non-High Density Lipoprotein Cholesterol [ Time Frame: Baseline, 24 weeks, and 76 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Apolipoprotein B [ Time Frame: Baseline, 24 weeks, and 76 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Apolipoprotein A-1 [ Time Frame: Baseline, 24 weeks, and 76 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Low Density Lipoprotein Cholesterol [ Time Frame: Baseline, 24 weeks, and 76 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 1500
Study Start Date: March 2008
Estimated Study Completion Date: November 2016
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anacetrapib
Participants randomly assigned to anacetrapib in base study will continue same treatment if enrolled in study extension.
Drug: anacetrapib
Participants will receive one tablet of anacetrapib 100 mg once daily for 76 weeks.
Other Names:
  • anacetrapib
  • MK0859
Placebo Comparator: Placebo
Participants randomly assigned to placebo in base study will continue same treatment if enrolled in study extension.
Drug: Comparator: placebo
Participants will receive one placebo tablet once daily for 76 weeks.

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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00685776

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00685776     History of Changes
Other Study ID Numbers: 0859-019, 2007_648
Study First Received: May 23, 2008
Last Updated: October 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
CHD/CHD risk-equivalent disease
Coronary Heart Disease (CHD)

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Anacetrapib
Oxazolidinones
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 16, 2014