Efficacy and Safety Study of Ezetimibe (SCH 58235, MK-0653) in Addition to Atorvastatin in Participants With Coronary Heart Disease or Multiple Cardiovascular Risk Factors (P00693/MK-0653-030)

A Phase 3 study testing Atorvastatin and Ezetimibe in people with Hypercholesterolemia, run by Organon and Co.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The overall objective is to evaluate the efficacy and safety of ezetimibe (SCH 058235/MK-0653) 10 mg administered daily in conjunction with atorvastatin in participants with Heterozygous Familial Hypercholesterolemia (HeFH) or in participants with coronary heart disease (CHD) or multiple cardiovascular risk factors… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hypercholesterolemia
What is being tested?: Atorvastatin and Ezetimibe
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 621 participants
Where: No sites listed yet
Study dates: 24 Apr 2000to 16 Nov 2001
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Primary hypercholesterolemic participants with known coronary heart disease (CHD) or multiple risk factors for CHD (≥2) not meeting the target low-density-lipoprotein cholesterol (LDL-C) of ≤100 mg/dL (2.59 mmol/L), with plasma LDL-C ≥130 mg/dL (3.37 mmol/L) and plasma triglycerides (TG) ≤350 mg/dL (3.99 mmol/L) while on starting-dose (10 mg) atorvastatin at least 4 weeks before initial qualifying lipid determination.
Participants with heterozygous familial hypercholesterolemia (HeFH) not meeting the target LDL-C of ≤100 mg/dL (2.59 mmol/L), with plasma LDL-C ≥130 mg/dL (3.37 mmol/L) and plasma TG ≤350 mg/dL (3.99 mmol/L) while on starting-dose (10 mg) atorvastatin for at least 4 weeks before initial lipid qualifying determination. HeFH is defined by: a) genetic testing; or b) LDL-C >190 mg/dL (4.9 mmol/L) and at least one of the following: (1) xanthomata in first or second degree relative; (2) family history of myocardial infarction under age 60 years in a first degree relative or family history of myocardial infarction under age 50 years in a second degree relative; (3) family history of total cholesterol (TC) >290 mg/dL (>7.5 mmol/L) in a first or second degree relative.
All women must have a negative pregnancy test prior to study entry. Women of child-bearing potential must agree to practice an effective barrier method of birth control for the duration of the study, as well as for 1 month following study completion.
Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable estrogen replacement therapy (ERT), estrogen/progestin hormone replacement therapy (HRT) or raloxifene regimen during the study period.
Participants 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.

Who cannot join

Individuals with a history of mental instability, drug/alcohol abuse within the past 5 years or individuals who have been treated or are being treated for severe psychiatric illness which in the opinion of the Investigator, may interfere with optimal participation in the study.
Underlying disease likely to limit life span to less than 1 year.
Participants who have previously been randomized in any of the studies evaluating ezetimibe.
Participants with known hypersensitivity or any contraindication to atorvastatin
Pregnant or lactating women.
Participants with congestive heart failure New York Heart Association (NYHA) Class III or IV.

Show all 17Show fewer

Participants with uncontrolled cardiac arrhythmias
Participants with myocardial infarction, coronary bypass surgery or angioplasty within 3 months of study entry.
Participants with unstable or severe peripheral artery disease within 3 months of study entry.
Participants with unstable angina pectoris.
Participants with disorders of the hematologic, digestive or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation.
Participants with uncontrolled (as determined by hemoglobin A1c [HbA1c]) or newly diagnosed (within 1 month of study entry) diabetes mellitus.
Participants with uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins. Clinically euthyroid participants on replacement doses of thyroid hormone are eligible for enrollment.
Participants with known impairment of renal function (creatinine >2.0 mg/dL), dysproteinemia, nephrotic syndrome or other renal disease (24-hour urinary protein 3+ or 1 gram).
Participants with active or chronic hepatobiliary or hepatic disease (participants with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 times the upper limit of the central laboratory reference range [ULN] will be excluded).
Participants who are known to be human immunodeficiency virus (HIV) positive.
Participants with known coagulopathy (prothrombin time [PT] or partial thromboplastin time [PTT] at Visit 2 >1.25 times control).

About this study

Official title: A Phase III Double-Blind Efficacy and Safety of Ezetimibe (SCH 58235) 10 MG in Addition to Atorvastatin in Subjects With Coronary Heart Disease or Multiple Cardiovascular Risk Factors and With Primary Hypercholesterolemia Not Controlled by a Starting Dose (10 mg) of Atorvastatin

The primary hypothesis is that the coadministration of ezetimibe 10 mg/day with atorvastatin therapy will result in a significantly greater proportion of participants achieving target low-density lipoprotein cholesterol (LDL-C) (≤100 mg/dL) when compared to the atorvastatin administered alone.

Conditions: Hypercholesterolemia
Being tested: Atorvastatin, Ezetimibe, Placebo for Ezetimibe, Placebo for Atorvastatin
Medical subject headings: Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AtorvastatinDrug
Also called LIPITOR®, SCH 412387, MK-9396
Atorvastatin administered orally QD as 10 mg tablets.
EzetimibeDrug
Also called ZETIA®, SCH 058235, MK-0653
Ezetimibe administered orally QD as 10 mg tablets
Placebo for EzetimibeDrug
Single placebo tablet administered orally QD
Placebo for AtorvastatinDrug
Single placebo tablet administered orally QD

Study groups in NCT03867318
Study group	Role	What they receive
Atorvastatin Monotherapy	Experimental	Participants receive double-blind atorvastatin 10 mg once daily (QD) via oral tablet PLUS open-label atorvastatin 10 mg QD via oral tablet for the entire duration of the study. Double-blind atorvastatin is to be added to the regimen for participants not achieving LDL-C target (≤100 mg/dL; 2.59 mmol/L). The maximum possible total daily dose of atorvastatin received in this group is 80 mg (10 mg open label plus 70 mg double blind). Receives: Drug: Atorvastatin; Drug: Placebo for Atorvastatin
Ezetimibe + Atorvastatin	Experimental	Participants receive double-blind ezetimibe 10 mg QD via oral tablet PLUS open-label atorvastatin 10 mg QD via oral tablet for the entire duration of the study. Double-blind atorvastatin is to be added to the regimen for participants not achieving LDL-C target (≤100 mg/dL; 2.59 mmol/L). The maximum possible total daily dose of atorvastatin received in this group is 40 mg (10 mg open label plus 30 mg double blind). Receives: Drug: Atorvastatin; Drug: Ezetimibe; Drug: Placebo for Ezetimibe; Drug: Placebo for Atorvastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants Achieving Target Low-Density-Lipoprotein Cholesterol (LDL-C) Levels of ≤100 mg/dL
The percentage of participants achieving the target low-density-lipoprotein cholesterol (LDL-C) levels (≤100 mg/dL [2.59 mmol/L]) as determined from blood samples following a standard ultracentrifugation/precipitation procedure (β-quantification).
Measured: Week 14
Percentage of Participants With an Adverse Event
An adverse event (AE) is defined as any physical or clinical change or disease reported by a participant or observed by the investigator or member of the staff at any time during the study, regardless of potential relationship to study treatment, and included onset or discovery of new illness and exacerbation of any pre-existing condition.
Measured: 14 weeks (Up to 16 weeks)
Percentage of Participants Who Discontinued the Study due to an Adverse Event
An adverse event (AE) is defined as any physical or clinical change or disease reported by a participant or observed by the investigator or member of the staff at any time during the study, regardless of potential relationship to study treatment, and included onset or discovery of new illness and exacerbation of any pre-existing condition.
Measured: 14 weeks (Up to 16 weeks)

Secondary outcomes (6)

Percentage of Participants Achieving Target LDL-C level (≤100 mg/dL)
The percentage of participants achieving the target low-density-lipoprotein cholesterol (LDL-C) levels (≤100 mg/dL [2.59 mmol/L]) as determined from blood samples following a standard ultracentrifugation/precipitation procedure (β-quantification).
Measured: Week 4
Mean Percent Change from Baseline in Direct LDL-C
Participants are to have their direct LDL-C levels assessed at baseline and after 4 weeks of study drug administration. The change from baseline will be calculated.
Measured: Baseline and Week 4
Mean Percent Changes from Baseline for Calculated LDL-C
Participants are to have their calculated LDL-C levels assessed at baseline and after 4 weeks of study drug administration. The change from baseline will be calculated.
Measured: Baseline and Week 4
Mean Percent Changes from Baseline for Total Cholesterol (TC)
Participants are to have their TC levels assessed at baseline and after 4 weeks of study drug administration. The change from baseline will be calculated.
Measured: Baseline and Week 4
Mean Percent Changes from Baseline for Triglycerides (TG)
Participants are to have their TG levels assessed at baseline and after 4 weeks of study drug administration. The change from baseline will be calculated.
Measured: Baseline and Week 4
Mean Percent Changes from Baseline for High-Density-Lipoprotein Cholesterol (HDL-C)
Participants hare to have their HDL-C levels assessed at baseline and after 4 weeks of study drug administration. The change from baseline will be calculated.
Measured: Baseline and Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Apr 200016 Nov 2001

First posted7 Mar 2019
Study start24 Apr 2000
Primary completion16 Nov 2001
Study completion16 Nov 2001

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 621 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03867318
Sponsor's protocol ID: P00693
Other IDs: MK-0653-030, P00693
Status last verified: Feb 2022
First submitted: 6 Mar 2019
Last updated: 10 May 2024
Results posted: No
Data monitoring committee: No
Individual data sharing: No

Publications

Stein E, Stender S, Mata P, Sager P, Ponsonnet D, Melani L, Lipka L, Suresh R, Maccubbin D, Veltri E; Ezetimibe Study Group. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J. 2004 Sep;148(3):447-55. doi: 10.1016/j.ahj.2004.03.052.
PubMed 15389231

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingObservational study
Causes and Natural History of Dyslipidemias
Hypercholesterolemia, Atherosclerosis
Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia

All Hypercholesterolemia trials

Study at a glance

From the registry record, last updated by the sponsor on 10 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III Double-Blind Efficacy and Safety of Ezetimibe (SCH 58235) 10 MG in Addition to Atorvastatin in Subjects With Coronary Heart Disease or Multiple Cardiovascular Risk Factors and With Primary Hypercholesterolemia Not Controlled by a Starting Dose (10 mg) of Atorvastatin
ClinicalTrials.gov ID: NCT03867318
Acronym / sponsor ID: P00693
Conditions: Hypercholesterolemia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 621 participants (actual)
Lead sponsor: Organon and CoIndustry (pharma, biotech, devices)
Study start: 24 Apr 2000 (actual)
Primary completion: 16 Nov 2001 (actual)
Study completion: 16 Nov 2001 (actual)
First posted: 7 Mar 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Atorvastatin Monotherapy	Experimental	Drug: Atorvastatin, Drug: Placebo for AtorvastatinParticipants receive double-blind atorvastatin 10 mg once daily (QD) via oral tablet PLUS open-label atorvastatin 10 mg QD via oral tablet for the entire duration of the study. Double-blind atorvastatin is to be added to the regimen for participants not achieving LDL-C target (≤100 mg/dL; 2.59 mmol/L). The maximum possible total daily dose of atorvastatin received in this group is 80 mg (10 mg open label plus 70 mg double blind).
Ezetimibe + Atorvastatin	Experimental	Drug: Atorvastatin, Drug: Ezetimibe, Drug: Placebo for Ezetimibe, Drug: Placebo for AtorvastatinParticipants receive double-blind ezetimibe 10 mg QD via oral tablet PLUS open-label atorvastatin 10 mg QD via oral tablet for the entire duration of the study. Double-blind atorvastatin is to be added to the regimen for participants not achieving LDL-C target (≤100 mg/dL; 2.59 mmol/L). The maximum possible total daily dose of atorvastatin received in this group is 40 mg (10 mg open label plus 30 mg double blind).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Primary hypercholesterolemic participants with known coronary heart disease (CHD) or multiple risk factors for CHD (≥2) not meeting the target low-density-lipoprotein cholesterol (LDL-C) of ≤100 mg/dL (2.59 mmol/L), with plasma LDL-C ≥130 mg/dL (3.37 mmol/L) and plasma triglycerides (TG) ≤350 mg/dL (3.99 mmol/L) while on starting-dose (10 mg) atorvastatin at least 4 weeks before initial qualifying lipid determination.
Participants with heterozygous familial hypercholesterolemia (HeFH) not meeting the target LDL-C of ≤100 mg/dL (2.59 mmol/L), with plasma LDL-C ≥130 mg/dL (3.37 mmol/L) and plasma TG ≤350 mg/dL (3.99 mmol/L) while on starting-dose (10 mg) atorvastatin for at least 4 weeks before initial lipid qualifying determination. HeFH is defined by: a) genetic testing; or b) LDL-C >190 mg/dL (4.9 mmol/L) and at least one of the following: (1) xanthomata in first or second degree relative; (2) family history of myocardial infarction under age 60 years in a first degree relative or family history of myocardial infarction under age 50 years in a second degree relative; (3) family history of total cholesterol (TC) >290 mg/dL (>7.5 mmol/L) in a first or second degree relative.
All women must have a negative pregnancy test prior to study entry. Women of child-bearing potential must agree to practice an effective barrier method of birth control for the duration of the study, as well as for 1 month following study completion.
Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable estrogen replacement therapy (ERT), estrogen/progestin hormone replacement therapy (HRT) or raloxifene regimen during the study period.
Participants 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.

Key exclusion criteria (17 listed)

Individuals with a history of mental instability, drug/alcohol abuse within the past 5 years or individuals who have been treated or are being treated for severe psychiatric illness which in the opinion of the Investigator, may interfere with optimal participation in the study.
Underlying disease likely to limit life span to less than 1 year.
Participants who have previously been randomized in any of the studies evaluating ezetimibe.
Participants with known hypersensitivity or any contraindication to atorvastatin
Pregnant or lactating women.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AtorvastatinAlso: LIPITOR®, SCH 412387, MK-9396Atorvastatin administered orally QD as 10 mg tablets.	Drug	Atorvastatin Monotherapy, Ezetimibe + Atorvastatin
EzetimibeAlso: ZETIA®, SCH 058235, MK-0653Ezetimibe administered orally QD as 10 mg tablets	Drug	Ezetimibe + Atorvastatin
Placebo for EzetimibeSingle placebo tablet administered orally QD	Drug	Ezetimibe + Atorvastatin
Placebo for AtorvastatinSingle placebo tablet administered orally QD	Drug	Atorvastatin Monotherapy, Ezetimibe + Atorvastatin

Primary outcome

Percentage of Participants Achieving Target Low-Density-Lipoprotein Cholesterol (LDL-C) Levels of ≤100 mg/dL
Time frame: Week 14
The percentage of participants achieving the target low-density-lipoprotein cholesterol (LDL-C) levels (≤100 mg/dL [2.59 mmol/L]) as determined from blood samples following a standard ultracentrifugation/precipitation procedure (β-quantification).
Percentage of Participants With an Adverse Event
Time frame: 14 weeks (Up to 16 weeks)
An adverse event (AE) is defined as any physical or clinical change or disease reported by a participant or observed by the investigator or member of the staff at any time during the study, regardless of potential relationship to study treatment, and included onset or discovery of new illness and exacerbation of any pre-existing condition.
Percentage of Participants Who Discontinued the Study due to an Adverse Event
Time frame: 14 weeks (Up to 16 weeks)
An adverse event (AE) is defined as any physical or clinical change or disease reported by a participant or observed by the investigator or member of the staff at any time during the study, regardless of potential relationship to study treatment, and included onset or discovery of new illness and exacerbation of any pre-existing condition.

6 secondary outcomes

Percentage of Participants Achieving Target LDL-C level (≤100 mg/dL)
Time frame: Week 4
Mean Percent Change from Baseline in Direct LDL-C
Time frame: Baseline and Week 4
Mean Percent Changes from Baseline for Calculated LDL-C
Time frame: Baseline and Week 4
Mean Percent Changes from Baseline for Total Cholesterol (TC)
Time frame: Baseline and Week 4
Mean Percent Changes from Baseline for Triglycerides (TG)
Time frame: Baseline and Week 4
Mean Percent Changes from Baseline for High-Density-Lipoprotein Cholesterol (HDL-C)
Time frame: Baseline and Week 4

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2024.
Results publication: PubMed 15389231Stein E, Stender S, Mata P, Sager P, Ponsonnet D, Melani L, Lipka L, Suresh R, Maccubbin D, Veltri E; Ezetimibe Study Group. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J. 2004 Sep;148(3):447-55. doi: 10.1016/j.ahj.2004.03.052.
Individual participant dataSharing planned: No

Related trials for Hypercholesterolemia

Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingObservational study
Causes and Natural History of Dyslipidemias
Hypercholesterolemia, Atherosclerosis
Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Atorvastatin and Ezetimibe in people with Hypercholesterolemia, run by Organon and Co.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Achieving Target Low-Density-Lipoprotein Cholesterol (LDL-C) Levels of ≤100 mg/dL (time frame: Week 14). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03867318, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2024.