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An Efficacy and Safety Study of Ezetimibe (MK-0653, SCH 58235) in Addition to Atorvastatin Compared to Placebo in Participants With Primary Hypercholesterolemia (MK-0653-013)

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ClinicalTrials.gov Identifier: NCT03867110
Recruitment Status : Completed
First Posted : March 7, 2019
Last Update Posted : June 13, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE March 6, 2019
First Posted Date  ICMJE March 7, 2019
Last Update Posted Date June 13, 2019
Actual Study Start Date  ICMJE March 6, 2000
Actual Primary Completion Date July 27, 2001   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 6, 2019)
Percent Change from Baseline at Week 12 of Plasma Low Density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Baseline and Week 12 ]
Plasma LDL-C determined following a standard ultracentrifugation / precipitation (quantification) procedure (direct LDL-C). Participants had LDL-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03867110 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2019)
  • Percent Change from Baseline at Week 12 for Calculated Low Density Lipoprotein-Cholesterol (LDL-C) [ Time Frame: Baseline and Week 12 ]
    Participants had LDL-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
  • Percent Change from Baseline at Week 12 for Total Cholesterol (TC) [ Time Frame: Baseline and Week 12 ]
    Participants had TC levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
  • Percent Change from Baseline at Week 12 for Triglycerides (TG) [ Time Frame: Baseline and Week 12 ]
    Participants had TG levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
  • Percent Change from Baseline at Week 12 for High Density-Lipoprotein-Cholesterol (HDL-C) [ Time Frame: Baseline and Week 12 ]
    Participants had HDL-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
  • Percent Change from Baseline at Week 12 for Apolipoprotein B (Apo B) [ Time Frame: Baseline and Week 12 ]
    Participants had Apo B levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
  • Percent Change from Baseline at Week 12 for Non-High Density-Lipoprotein-Cholesterol (Non-HDL-C) [ Time Frame: Baseline and Week 12 ]
    Participants had Non-HDL-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
  • Percent Change from Baseline at Week 12 for High Density-Lipoprotein 2-Cholesterol (HDL2-C) [ Time Frame: Baseline and Week 12 ]
    Participants had HDL2-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
  • Percent Change from Baseline at Week 12 for High Density-Lipoprotein 3-Cholesterol (HDL3-C) [ Time Frame: Baseline and Week 12 ]
    Participants had HDL3-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
  • Percent Change from Baseline at Week 12 for Apolipoprotein A-I (Apo A-I), [ Time Frame: Baseline and Week 12 ]
    Participants had Apo A1 levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
  • Percent Change from Baseline at Week 12 for Direct Low Density-Lipoprotein 3-Cholesterol/High Density-Lipoprotein 3-Cholesterol (LDL-C/HDL-C) Ratio [ Time Frame: Baseline and Week 12 ]
    Participants had LDL-C and HDL-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline in the LDL-C/HDL-C ratio was calculated.
  • Percent Change from Baseline at Week 12 for Direct Total Cholesterol/High Density-Lipoprotein 3-Cholesterol (TC/HDL-C) Ratio [ Time Frame: Baseline and Week 12 ]
    Participants had TC and HDL-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline in the TC/HDL-C ratio was calculated.
  • Percent Change from Baseline at Week 12 for Lipoprotein (a) (Lp[a]) [ Time Frame: Baseline and Week 12 ]
    Participants had Lp(a) levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
  • The Percentage of Participants Achieving National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP II) Target Goal for Direct Low Density Lipoprotein-Cholesterol (LDL-C) [ Time Frame: Week 12 ]
    LDL cholesterol level goal is <100 mg per deciliter (2.60 mmol per L)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Efficacy and Safety Study of Ezetimibe (MK-0653, SCH 58235) in Addition to Atorvastatin Compared to Placebo in Participants With Primary Hypercholesterolemia (MK-0653-013)
Official Title  ICMJE A Phase 3, Double-Blind Efficacy and Safety Study of Ezetimibe (SCH 58235) 10 mg in Addition to Atorvastatin Compared to Placebo in Subjects With Primary Hypercholesterolemia (Protocol P00692)
Brief Summary This is a multicenter, randomized, double-blind, placebo-controlled, balanced-parallel-group, efficacy and safety trial of ezetimibe coadministered with atorvastatin in adult participants with primary hypercholesterolemia. The primary hypothesis is that the coadministration of ezetimibe 10 mg/day with atorvastatin (pooled across all doses: 10 mg, 20 mg, 40 mg, 80 mg) will result in a significantly greater reduction in direct low density lipoprotein-cholesterol (LDL-C) when compared with atorvastatin (pooled across all doses: 10 mg, 20 mg, 40 mg, 80 mg) alone and ezetimibe 10 mg alone.
Detailed Description Not Provided
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 Hypercholesterolemia
Intervention  ICMJE
  • Drug: Placebo
  • Drug: Ezetimibe 10 mg
    Other Names:
    • MK-0653
    • SCH 58235
    • ZETIA®
  • Drug: Atorvastatin 10 mg
    Other Name: LIPITOR®
  • Drug: Atorvastatin 20 mg
    Other Name: LIPITOR®
  • Drug: Atorvastatin 40 mg
    Other Name: LIPITOR®
  • Drug: Atorvastatin 80 mg
    Other Name: LIPITOR®
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo is to be taken orally once a day (QD) in the morning for 12 consecutive weeks.
    Intervention: Drug: Placebo
  • Active Comparator: Ezetimibe 10 mg
    Ezetimibe 10 mg (MK-0653, SCH 58235) is to be taken orally QD in the morning for 12 consecutive weeks.
    Intervention: Drug: Ezetimibe 10 mg
  • Active Comparator: Atorvastatin 10 mg
    Atorvastatin 10 mg is to be taken orally QD in the morning for 12 consecutive weeks.
    Intervention: Drug: Atorvastatin 10 mg
  • Experimental: Ezetimibe 10 mg + Atorvastatin 10 mg
    Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 10 mg is to be taken orally QD in the morning for 12 consecutive weeks.
    Interventions:
    • Drug: Ezetimibe 10 mg
    • Drug: Atorvastatin 10 mg
  • Active Comparator: Atorvastatin 20 mg
    Atorvastatin 20 mg is to be taken orally QD in the morning for 12 consecutive weeks.
    Intervention: Drug: Atorvastatin 20 mg
  • Experimental: Ezetimibe 10 mg + Atorvastatin 20 mg
    Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 20 mg is to be taken orally QD in the morning for 12 consecutive weeks.
    Interventions:
    • Drug: Ezetimibe 10 mg
    • Drug: Atorvastatin 20 mg
  • Active Comparator: Atorvastatin 40 mg
    Atorvastatin 40 mg is to be taken orally QD in the morning for 12 consecutive weeks.
    Intervention: Drug: Atorvastatin 40 mg
  • Experimental: Ezetimibe 10 mg + Atorvastatin 40 mg
    Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 40 mg is to be taken orally QD in the morning for 12 consecutive weeks.
    Interventions:
    • Drug: Ezetimibe 10 mg
    • Drug: Atorvastatin 40 mg
  • Active Comparator: Atorvastatin 80 mg
    Atorvastatin 80 mg is to be taken orally QD in the morning for 12 consecutive weeks.
    Intervention: Drug: Atorvastatin 80 mg
  • Experimental: Ezetimibe 10 mg + Atorvastatin 80 mg
    Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 80 mg is to be taken orally QD in the morning for 12 consecutive weeks.
    Interventions:
    • Drug: Ezetimibe 10 mg
    • Drug: Atorvastatin 80 mg
Publications * Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, Sun S, LeBeaut AP, Sager PT, Veltri EP; Ezetimibe Study Group. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation. 2003 May 20;107(19):2409-15. Epub 2003 Apr 28.

*   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: March 6, 2019)
628
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 27, 2001
Actual Primary Completion Date July 27, 2001   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • If female, is not pregnant or breastfeeding, and is either not a woman of childbearing potential (WOCBP), or is a WOCBP who has used a contraceptive consistent with local regulations.
  • Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable estrogen (ERT), estrogen/progestin (HRT) or raloxifene regimen during the study period.
  • Primary hypercholesterolemic participants with a plasma LDL-Cholesterol ≥145 mg/dL (3.75 mmol/L) and ≤250 mg/dL (6.48 mmol/L) and plasma triglyceride ≤350 mg/dL (3.99 mmol/L) after adequate drug washout
  • Must be willing to observe the National Cholesterol Education Program (NCEP) Step I diet as determined by a Ratio of Ingested Saturated fat and Cholesterol to Calories (RISCC) score not greater than 24 throughout this study. Ability to complete Diet Diaries needs to be demonstrated.

Exclusion Criteria:

  • Has a history of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy.
  • Underlying disease likely to limit life span to less than 1 year.
  • Participants with hypercholesterolemia in whom withholding of approved lipid-lowering therapy would be inappropriate.
  • Have previously been randomized in any of the studies evaluating Ezetimibe (SCH 58235).
  • Known hypersensitivity or any contraindication to atorvastatin (LIPITOR®).
  • Pregnant or lactating women.
  • Congestive heart failure New York Heart Association (NYHA) Class III or IV.
  • Uncontrolled cardiac arrhythmias.
  • Myocardial infarction, coronary bypass surgery or angioplasty within 6 months of study entry.
  • Unstable or severe peripheral artery disease within 3 months of study entry.
  • Unstable angina pectoris.
  • Disorders of the hematologic, digestive or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation.
  • Uncontrolled or newly diagnosed (within 1 month of study entry) diabetes mellitus.
  • Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins.
  • Known impairment of renal function (plasma creatinine >2.0 mg/dL), dysproteinemia, nephrotic syndrome or other renal disease.
  • Active or chronic hepatobiliary or hepatic disease.
  • Participants who are known to be Human Immunodeficiency Virus (HIV) positive.
  • Participants with known coagulopathy.
  • Lipid-altering agents, other than study drugs for the whole duration of the study.
  • Oral corticosteroids.
  • Cardiovascular drugs such as: beta blockers, calcium channel blockers, ACE inhibitors, nitrates or α-adrenergic blockers or thiazide diuretics will be allowed, provided the dose remains constant for the duration of the study and the participant has received a stable dose for at least 8 weeks before the initial qualifying LDL-C level is drawn. Aspirin up to 325 mg/day is permitted. In addition, aspirin is allowed as a as needed (prn) concomitant medication.
  • Treatment with psyllium or other fiber-based laxatives unless treated with a stable regimen for at least 4 weeks before initial qualifying lipid determination. Dose must remain constant throughout the study period.
  • Treatment with troglitazone (Rezulin®) unless treated with a stable regimen for at least 6 weeks before initial qualifying lipid determination. Dose must remain constant throughout the study period.
  • Treatment with cyclosporine.
  • Use of any investigational drugs within 30 days of study entry.
  • Treatment with agents with known drug interaction with atorvastatin including antifungal azoles (itraconazole and ketoconazole), macrolide antibiotics (erythromycin and clarithromycin), and nefazodone. In addition, treatment with other agents that may interfere with or induce the CYP3A4 isoenzyme of the cytochrome P450 system should be avoided.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (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  
 
Administrative Information
NCT Number  ICMJE NCT03867110
Other Study ID Numbers  ICMJE P00692
MK-0653-013 ( Other Identifier: Merck Protocol Number )
P00692 ( Other Identifier: Schering-Plough Protocol Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date June 2019

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