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

Sponsor:	Merck
Information provided by:	Merck
ClinicalTrials.gov Identifier:	NCT00685776

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 III

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:

MedlinePlus related topics: Cholesterol Coronary Artery Disease Heart Diseases Potassium Statins

U.S. FDA Resources

Further study details as provided by Merck:

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:	April 2008
Estimated Study Completion Date:	February 2013
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 anacetrapib	Drug: anacetrapib Patients will receive one tablet of anacetrapib 100 mg once daily for 76 weeks. Other Names: anacetrapib MK0859
Placebo Comparator: 2 placebo	Drug: Comparator: placebo Patients 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.

ACRONYM: DEFINE= Determining the EFficacy and Tolerability of 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

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

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

No publications provided by Merck

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2010 Nov 17.

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.

Responsible Party:	Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00685776 History of Changes
Other Study ID Numbers:	MK-0859-019, 2007_648
Study First Received:	May 23, 2008
Last Updated:	April 6, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Merck:

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

Oxazolidinones
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012