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A Study of SCH 58235 (Ezetimibe) When Added to Ongoing Therapy With a Statin in Participants With Primary Hypercholesterolemia, Known Coronary Heart Disease, or Multiple Cardiovascular Risk Factors (P02173)

Primary Purpose

Primary Hypercholesterolemia

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Ezetimibe
Placebo
Simivastatin
Statin
Sponsored by
Organon and Co
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Hypercholesterolemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  • Currently taking an approved and stable (for at least 6 weeks prior to screening) daily dose of a statin and by history had taken >80% of daily doses for the preceding 6 weeks
  • Have a negative pregnancy test
  • Agree to practice an effective barrier method of birth control during the study if of childbearing potential
  • Females receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives, maintain a stable dose and regimen for at least 8 weeks and be willing to continue the same regimen for the duration of the study
  • Must verify previous instruction on an National Cholesterol Education Program (NCEP) Step 1 diet or similar diet and must maintain a stable diet regimen for the duration of the study
  • Weight stability ( ± 2 kg) for at least 6 weeks prior to entry into the study Exclusion Criteria
  • History of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy
  • Previously enrolled to any study evaluating ezetimibe
  • Pregnant or lactating
  • Consumes greater than 14 alcoholic drinks/week
  • Taking a lipid-altering agent (other than statins) in previous 6 weeks
  • Taking Oral corticosteroids, unless the corticosteroids were for replacement therapy to treat pituitary/adrenal disease and were treated with a stable regimen for at least the previous 6 weeks
  • Treatment with psyllium, other fiber-based laxatives, and other over-the-counter (OTC) therapies that affect serum lipids, unless treated with a stable regimen for at least 6 weeks
  • Taking orlistat
  • Taking cyclosporine
  • Use of any investigational drugs within 30 days
  • Treatment with agents with known interactions with statins including antifungal azoles (itraconazole and ketoconazole), macrolide antibiotics (erythromycin and clarithromycin) and nefazodone or with other potent agents that could significantly interfere with cytochrome P-450 system
  • Congestive heart failure New York Heart Association (NYHA) Class III or IV
  • Uncontrolled cardiac arrhythmias
  • Myocardial infarction, coronary artery bypass surgery or angioplasty within 3 months
  • Unstable or severe peripheral artery disease within 3 months
  • 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
  • Poorly controlled or newly diagnosed (within 3 months) diabetes mellitus, or change in antidiabetic pharmacotherapy (i.e., change in dosage [with the exception of ± 10 units of insulin] or addition of new medication) within 3 months
  • Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (i.e., secondary causes of hyperlipidemia). Clinically euthyroid participants on replacement doses of thyroid hormone are eligible for enrollment if thyroid stimulating hormone (TSH) is within the normal range
  • Impaired renal function, nephrotic syndrome, or other renal disease
  • Active or chronic hepatobiliary or hepatic disease
  • Positive for human immunodeficiency virus (HIV)
  • Cancer within the past 5 years (except for basal cell carcinoma)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Placebo Comparator

    Experimental

    Placebo Comparator

    Arm Label

    Ezetimibe: Base Study

    Placebo: Base Study

    Ezetimibe: Extension

    Placebo: Extension

    Arm Description

    10-mg tablet, oral taken once daily concomitantly with the participant' s current statin therapy for 8 weeks.

    Placebo for ezetimibe 10-mg tablet, oral taken once daily concomitantly with the participant' s current statin therapy for 8 weeks.

    10-mg tablet, oral taken once daily concomitantly with simvastatin for 48 weeks.

    Placebo for ezetimibe tablet, oral taken once daily concomitantly with simvastatin for 48 weeks.

    Outcomes

    Primary Outcome Measures

    Percentage Change from Baseline in LDL-C: Base Study
    Percentage Participants with Consecutive Elevations ≥3 x Upper Limit of Normal (ULN) in Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT): Extension

    Secondary Outcome Measures

    Percentage of Participants Achieving LDL-C National Cholesterol Education Program (NCEP) Adult Treatment Program II (ATP II) Target Levels: Base Study
    Percentage Change from Baseline in Total Cholesterol (TC) : Base Study
    Percentage Change from Baseline in Triglycerides (TG): Base Study
    Percentage Change from Baseline in High-density Lipoprotein-cholesterol (HDL-C) : Base Study
    Percentage Change from Baseline in Non-HDL-C: Base Study
    Percentage Change from Baseline in Apolipoprotein B (apoB) : Base Study
    Percentage Change from Baseline in Apolipoprotein A-I (Apo A-I) : Base Study
    Percentage Change from Baseline in Apolipoprotein A-II (Apo A-II) : Base Study
    Percentage Change from Baseline in LDL-C:HDL-C Ratio: Base Study
    Percentage Change from Baseline in Total-C:HDL-C Ratio: Base Study
    Change from Baseline in C-reactive Protein (CRP): Base Study
    Percentage Change from Baseline in LDL-C: Extension

    Full Information

    First Posted
    March 19, 2019
    Last Updated
    February 7, 2022
    Sponsor
    Organon and Co
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03882905
    Brief Title
    A Study of SCH 58235 (Ezetimibe) When Added to Ongoing Therapy With a Statin in Participants With Primary Hypercholesterolemia, Known Coronary Heart Disease, or Multiple Cardiovascular Risk Factors (P02173)
    Official Title
    A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Lipid-Altering Efficacy, Safety, and Tolerability of SCH 58235 When Added to Ongoing Therapy With an HMG-CoA Reductase Inhibitor (Statin) in Patients With Primary Hypercholesterolemia, Known Coronary Heart Disease, or Multiple Cardiovascular Risk Factors
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2022
    Overall Recruitment Status
    Completed
    Study Start Date
    January 31, 2001 (Actual)
    Primary Completion Date
    July 27, 2001 (Actual)
    Study Completion Date
    July 27, 2001 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Organon and Co

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a study to evaluate the lipid-altering efficacy, safety, and tolerability of ezetimibe when added to ongoing therapy with an 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) in participants with primary hypercholesterolemia, multiple cardiovascular risk factors, or known coronary heart disease (CHD) or CHD-equivalent disease. The statin and dose in use by the participant at screening will be maintained at the same dose for the 8-week treatment phase of the study. Following the treatment, there will be a 6-week cholesterol reversibility phase to determine the rebound effect on cholesterol after ezetimibe is discontinued, but the participant is still on their statin therapy. The primary hypothesis is that the addition of ezetimibe 10 mg/day to ongoing statin monotherapy will result in a further reduction in low-density lipoprotein-cholesterol (LDL-C) compared with placebo. The protocol was amended to include an extension for participants who complete the base study. The extension will evaluate the safety and tolerability of concomitant treatment of simvastatin with ezetimibe10 mg/day over a 1-year period. All participants in the extension will be converted from current statin to an equivalent dose of simvastatin for 6 weeks. Participants then will be randomly assigned to receive simvastatin coadministered with either with Ezetimibe 10 mg daily or matching placebo for the reminder of study.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Primary Hypercholesterolemia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    769 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Ezetimibe: Base Study
    Arm Type
    Experimental
    Arm Description
    10-mg tablet, oral taken once daily concomitantly with the participant' s current statin therapy for 8 weeks.
    Arm Title
    Placebo: Base Study
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo for ezetimibe 10-mg tablet, oral taken once daily concomitantly with the participant' s current statin therapy for 8 weeks.
    Arm Title
    Ezetimibe: Extension
    Arm Type
    Experimental
    Arm Description
    10-mg tablet, oral taken once daily concomitantly with simvastatin for 48 weeks.
    Arm Title
    Placebo: Extension
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo for ezetimibe tablet, oral taken once daily concomitantly with simvastatin for 48 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Ezetimibe
    Intervention Description
    10 mg tablet, oral, once daily
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    one tablet, oral, once daily
    Intervention Type
    Drug
    Intervention Name(s)
    Simivastatin
    Intervention Description
    Once daily administration at dose to be determined
    Intervention Type
    Drug
    Intervention Name(s)
    Statin
    Intervention Description
    Statin administered orally once daily at dose determined by treatment prior to enrollment by personal physician
    Primary Outcome Measure Information:
    Title
    Percentage Change from Baseline in LDL-C: Base Study
    Time Frame
    Baseline and Week 8 of Base Study
    Title
    Percentage Participants with Consecutive Elevations ≥3 x Upper Limit of Normal (ULN) in Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT): Extension
    Time Frame
    up to 48 weeks (Extension)
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants Achieving LDL-C National Cholesterol Education Program (NCEP) Adult Treatment Program II (ATP II) Target Levels: Base Study
    Time Frame
    Week 8 of Base Study
    Title
    Percentage Change from Baseline in Total Cholesterol (TC) : Base Study
    Time Frame
    Baseline and Week 8 of Base Study
    Title
    Percentage Change from Baseline in Triglycerides (TG): Base Study
    Time Frame
    Baseline and Week 8 of Base Study
    Title
    Percentage Change from Baseline in High-density Lipoprotein-cholesterol (HDL-C) : Base Study
    Time Frame
    Baseline and Week 8 of Base Study
    Title
    Percentage Change from Baseline in Non-HDL-C: Base Study
    Time Frame
    Baseline and Week 8 of Base Study
    Title
    Percentage Change from Baseline in Apolipoprotein B (apoB) : Base Study
    Time Frame
    Baseline and Week 8 of Base Study
    Title
    Percentage Change from Baseline in Apolipoprotein A-I (Apo A-I) : Base Study
    Time Frame
    Baseline and Week 8 of Base Study
    Title
    Percentage Change from Baseline in Apolipoprotein A-II (Apo A-II) : Base Study
    Time Frame
    Baseline and Week 8 of Base Study
    Title
    Percentage Change from Baseline in LDL-C:HDL-C Ratio: Base Study
    Time Frame
    Baseline and Week 8 of Base Study
    Title
    Percentage Change from Baseline in Total-C:HDL-C Ratio: Base Study
    Time Frame
    Baseline and Week 8 of Base Study
    Title
    Change from Baseline in C-reactive Protein (CRP): Base Study
    Time Frame
    Baseline and Week 8 of Base Study
    Title
    Percentage Change from Baseline in LDL-C: Extension
    Time Frame
    Baseline (Week 6) and Week 18 of Extension

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria Currently taking an approved and stable (for at least 6 weeks prior to screening) daily dose of a statin and by history had taken >80% of daily doses for the preceding 6 weeks Have a negative pregnancy test Agree to practice an effective barrier method of birth control during the study if of childbearing potential Females receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives, maintain a stable dose and regimen for at least 8 weeks and be willing to continue the same regimen for the duration of the study Must verify previous instruction on an National Cholesterol Education Program (NCEP) Step 1 diet or similar diet and must maintain a stable diet regimen for the duration of the study Weight stability ( ± 2 kg) for at least 6 weeks prior to entry into the study Exclusion Criteria History of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy Previously enrolled to any study evaluating ezetimibe Pregnant or lactating Consumes greater than 14 alcoholic drinks/week Taking a lipid-altering agent (other than statins) in previous 6 weeks Taking Oral corticosteroids, unless the corticosteroids were for replacement therapy to treat pituitary/adrenal disease and were treated with a stable regimen for at least the previous 6 weeks Treatment with psyllium, other fiber-based laxatives, and other over-the-counter (OTC) therapies that affect serum lipids, unless treated with a stable regimen for at least 6 weeks Taking orlistat Taking cyclosporine Use of any investigational drugs within 30 days Treatment with agents with known interactions with statins including antifungal azoles (itraconazole and ketoconazole), macrolide antibiotics (erythromycin and clarithromycin) and nefazodone or with other potent agents that could significantly interfere with cytochrome P-450 system Congestive heart failure New York Heart Association (NYHA) Class III or IV Uncontrolled cardiac arrhythmias Myocardial infarction, coronary artery bypass surgery or angioplasty within 3 months Unstable or severe peripheral artery disease within 3 months 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 Poorly controlled or newly diagnosed (within 3 months) diabetes mellitus, or change in antidiabetic pharmacotherapy (i.e., change in dosage [with the exception of ± 10 units of insulin] or addition of new medication) within 3 months Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (i.e., secondary causes of hyperlipidemia). Clinically euthyroid participants on replacement doses of thyroid hormone are eligible for enrollment if thyroid stimulating hormone (TSH) is within the normal range Impaired renal function, nephrotic syndrome, or other renal disease Active or chronic hepatobiliary or hepatic disease Positive for human immunodeficiency virus (HIV) Cancer within the past 5 years (except for basal cell carcinoma)
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    15811480
    Citation
    Masana L, Mata P, Gagne C, Sirah W, Cho M, Johnson-Levonas AO, Meehan A, Troxell JK, Gumbiner B; Ezetimibe Study Group. Long-term safety and, tolerability profiles and lipid-modifying efficacy of ezetimibe coadministered with ongoing simvastatin treatment: a multicenter, randomized, double-blind, placebo-controlled, 48-week extension study. Clin Ther. 2005 Feb;27(2):174-84. doi: 10.1016/j.clinthera.2005.02.011.
    Results Reference
    result
    PubMed Identifier
    12423708
    Citation
    Gagne C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M, Cho M, Musliner TA, Gumbiner B; Ezetimibe Study Group. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol. 2002 Nov 15;90(10):1084-91. doi: 10.1016/s0002-9149(02)02774-1.
    Results Reference
    result

    Learn more about this trial

    A Study of SCH 58235 (Ezetimibe) When Added to Ongoing Therapy With a Statin in Participants With Primary Hypercholesterolemia, Known Coronary Heart Disease, or Multiple Cardiovascular Risk Factors (P02173)

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