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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00685776
Recruitment Status : Completed
First Posted : May 28, 2008
Last Update Posted : December 11, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Tracking Information
First Submitted Date  ICMJE May 23, 2008
First Posted Date  ICMJE May 28, 2008
Last Update Posted Date December 11, 2017
Actual Study Start Date  ICMJE March 24, 2008
Actual Primary Completion Date July 2, 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2010)
  • Change from baseline in Low Density Lipoprotein Cholesterol [ Time Frame: Baseline and 24 weeks ]
  • Number of participants with hepatitis-related adverse experiences [ Time Frame: Through 88 weeks ]
  • Number of participants with Alanine Transaminase consecutive elevations greater than or equal to 3xULN (Upper Limit of Normal) [ Time Frame: Through 88 weeks ]
  • Number of participants with Aspartate Aminotransferase consecutive elevations greater than or equal to 3xULN [ Time Frame: Through 88 weeks ]
  • Number of participants with Creatine Phosphokinase elevations greater than or equal to 10xULN [ Time Frame: Through 88 weeks ]
  • Number of participants with Creatine Phosphokinase elevations greater than or equal 10xULN with muscle symptoms [ Time Frame: Through 88 weeks ]
  • Number of participants with sodium, chloride, or bicarbonate elevations greater than ULN [ Time Frame: Through 88 weeks ]
  • Number of participants with reduction in potassium levels less than LLN (Lower Limit of Normal) [ Time Frame: Through 88 weeks ]
  • Number of participants with myalgia [ Time Frame: Through 88 weeks ]
  • Number of participants with rhabdomyolysis [ Time Frame: Through 88 weeks ]
  • Number of participants with pre-specified adjudicated cardiovascular serious adverse events [ Time Frame: Through 88 weeks ]
  • Number of participants with death from any cause [ Time Frame: Through 88 weeks ]
  • Number of participants with significant increase in Blood Pressure [ Time Frame: Through 88 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 27, 2008)
Reduction in LDL-C compared to placebo [ Time Frame: 24 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2010)
  • Change from baseline in High Density Lipoprotein Cholesterol [ Time Frame: Baseline, 24 weeks, and 76 weeks ]
  • Change from baseline in non-High Density Lipoprotein Cholesterol [ Time Frame: Baseline, 24 weeks, and 76 weeks ]
  • Change from baseline in Apolipoprotein B [ Time Frame: Baseline, 24 weeks, and 76 weeks ]
  • Change from baseline in Apolipoprotein A-1 [ Time Frame: Baseline, 24 weeks, and 76 weeks ]
  • Change from baseline in Low Density Lipoprotein Cholesterol [ Time Frame: Baseline, 24 weeks, and 76 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2008)
Increase in HDL-C, safety (adverse events, vital signs, ECG, physical exam, and laboratory tests) [ Time Frame: 76 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Assess the Tolerability and Efficacy of Anacetrapib in Patients With Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease (MK-0859-019)
Official Title  ICMJE 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
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.
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Coronary Heart Disease (CHD)
  • CHD Risk-Equivalent Disease
Intervention  ICMJE
  • Drug: anacetrapib
    Participants will receive one tablet of anacetrapib 100 mg once daily for 76 weeks.
    Other Name: MK0859
  • Drug: Comparator: placebo
    Participants will receive one placebo tablet once daily for 76 weeks.
Study Arms  ICMJE
  • Experimental: Anacetrapib
    Participants randomly assigned to anacetrapib in base study will continue same treatment if enrolled in study extension.
    Intervention: Drug: anacetrapib
  • Placebo Comparator: Placebo
    Participants randomly assigned to placebo in base study will continue same treatment if enrolled in study extension.
    Intervention: Drug: Comparator: placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 7, 2017)
1623
Original Estimated Enrollment  ICMJE
 (submitted: May 27, 2008)
1500
Actual Study Completion Date  ICMJE November 23, 2017
Actual Primary Completion Date July 2, 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Australia,   Austria,   Canada,   Colombia,   Finland,   France,   Germany,   Hong Kong,   Hungary,   Israel,   Malaysia,   Mexico,   Netherlands,   New Zealand,   Norway,   Russian Federation,   Spain,   Sweden,   United States
 
Administrative Information
NCT Number  ICMJE NCT00685776
Other Study ID Numbers  ICMJE 0859-019
2007_648 ( Other Identifier: Merck Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Merck Sharp & Dohme LLC
Original Responsible Party Executive Vice President, Clinical and Quantitative Sciences, Merck & Co., Inc.
Current Study Sponsor  ICMJE Merck Sharp & Dohme LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Merck Sharp & Dohme LLC
PRS Account Merck Sharp & Dohme LLC
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP