HypercholesterolemiaPhase 3NCT00782184

Ezetimibe/Simvastatin (10 mg/40 mg) vs. the Doubling of Atorvastatin in High Risk Participants (MK-0653A-134 AM1)(COMPLETED)

A Phase 3 study testing ezetimibe/simvastatin 10/40, atorvastatin 40 mg and atorvastatin 20 mg 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.

Official record

Search all trials

Trial summary

Participants currently taking atorvastatin 20 mg will be switched to either atorvastatin 40 mg or ezetimibe/simvastatin 10 mg/40 mg (10/40). After 6 weeks of treatment, the percent reduction in low-density lipoprotein cholesterol (LDL-C) will be assessed and compared between the two treatment groups. Read more about this study

Who is it for?: Ages 18 to 79 years
Conditions the study is for: Hypercholesterolemia
What is being tested?: ezetimibe/simvastatin 10/40, atorvastatin 40 mg and atorvastatin 20 mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 250 participants
Where: No sites listed yet
Study dates: Nov 2008to Sep 2010
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 to 79 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Participants who are either statin naive or on approved lipid lowering therapy for 6 weeks prior to study initiation
Participant meets Adult Treatment Panel (ATP) III High Risk criteria

Who cannot join

Females who are pregnant or breastfeeding
Participant consumes more than 14 alcoholic beverages per week
Participant has been treated with an investigational drug within the last 30 days
Participant has congestive heart failure (New York Heart Association [NYHA] Type III or IV)
Participant has had gastric bypass
Participant is newly diagnosed with type 1 or 2 diabetes
Participant is Human Immunodeficiency Virus (HIV) positive
Participant has a history of drug or alcohol abuse within the last 5 years

About this study

Official title: A Randomized, Double-Blind, Active-Controlled Study of Patients With Primary Hypercholesterolemia and High Cardiovascular Risk and Not Adequately Controlled With Atorvastatin: A Comparison of Switching to a Combination Tablet Ezetimibe/Simvastatin Versus Doubling the Baseline Dose of Atorvastatin

Conditions: Hypercholesterolemia
Being tested: ezetimibe/simvastatin 10/40, atorvastatin 40 mg, atorvastatin 20 mg
Medical subject headings: Hypercholesterolemia

What participants receive

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

ezetimibe/simvastatin 10/40Drug
Also called Vytorin
ezetimibe/simvastatin 10/40 tablet once daily for 6 weeks.
atorvastatin 40 mgDrug
Also called Lipitor
atorvastatin 40 mg tablet once daily for 6 weeks
atorvastatin 20 mgDrug
Also called Lipitor
All participants will take atorvastatin 20 mg tablet once daily for the 5 week run-in period before randomization

Study groups in NCT00782184
Study group	Role	What they receive
ezetimibe/simvastatin 10/40	Experimental	Participants received 20 mg open-label atorvastatin during a 5-week run-in period. Following this run-in period, ezetimibe/simvastatin 10/40 was administered once daily in tablet form during the 6-week double-blind treatment period Receives: Drug: ezetimibe/simvastatin 10/40; Drug: atorvastatin 20 mg
atorvastatin 40 mg	Active comparator	Participants received 20 mg open-label atorvastatin during a 5-week run-in period. Following this run-in period, 40 mg atorvastatin was administered once daily in tablet form during the 6-week double-blind treatment period Receives: Drug: atorvastatin 40 mg; Drug: atorvastatin 20 mg

What is being measured

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

Percent Change From Baseline in Low Density Lipoprotein (LDL)-C
Measured: Baseline (Treatment Day 1), Treatment Week 6

Secondary outcomes (14)

Number of Participants Reaching LDL-C Target Goals of <70 mg/dL
Target LDL-C level of < 70 mg/dL (1.81 mmol/L) at study endpoint after 6 weeks of treatment for the Full Analysis Set (FAS) population.
Measured: Treatment Week 6
Number of Participants Reaching LDL-C Target Goal <77 mg/dL
Target LDL-C level of < 77 mg/dL (2.00 mmol/L) at study endpoint after 6 weeks of treatment for the Full Analysis Set (FAS) population.
Measured: Treatment Week 6
Number of Participants Reaching LDL-C Target Goal <100 mg/dL
Target LDL-C level of < 100 mg/dL (2.59 mmol/L) at study endpoint after 6 weeks of treatment for the Full Analysis Set (FAS) population.
Measured: Treatment Week 6
Percent Change From Baseline in Total Cholesterol
Measured: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Triglycerides
Measured: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol
Measured: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Non-HDL Cholesterol
Measured: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in LDL-Cholesterol/HDL-Cholesterol Ratio
Measured: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Total Cholesterol/HDL-Cholesterol Ratio
Measured: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Non-HDL Cholesterol/HDL-Cholesterol Ratio
Measured: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Apolipoprotein B
Measured: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Apolipoprotein A-1
Measured: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Apolipoprotein B/A-1 Ratio
Measured: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in High-sensitivity C-Reactive Protein (Hs-CRP)
Measured: Baseline (Treatment Day 1), Treatment Week 6

Timeline

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

Nov 2008Sep 2010

First posted31 Oct 2008 (estimated)
Study startNov 2008
Primary completionSep 2010
Study completionSep 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
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: 250 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00782184
Sponsor's protocol ID: 0653A-134
Other IDs: 2008_576
Status last verified: Feb 2022
First submitted: 29 Oct 2008
Last updated: 16 May 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Publications

Hing Ling PK, Civeira F, Dan AG, Hanson ME, Massaad R, De Tilleghem Cle B, Milardo C, Triscari J. Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study. Lipids Health Dis. 2012 Jan 31;11:18. doi: 10.1186/1476-511X-11-18.
PubMed 22293030

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 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Active-Controlled Study of Patients With Primary Hypercholesterolemia and High Cardiovascular Risk and Not Adequately Controlled With Atorvastatin: A Comparison of Switching to a Combination Tablet Ezetimibe/Simvastatin Versus Doubling the Baseline Dose of Atorvastatin
ClinicalTrials.gov ID: NCT00782184
Acronym / sponsor ID: 0653A-134
Conditions: Hypercholesterolemia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 250 participants (actual)
Lead sponsor: Organon and CoIndustry (pharma, biotech, devices)
Study start: Nov 2008
Primary completion: Sep 2010 (actual)
Study completion: Sep 2010 (actual)
First posted: 31 Oct 2008 (estimated)
Results: Posted 31 Oct 2011

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
ezetimibe/simvastatin 10/40	Experimental	Drug: ezetimibe/simvastatin 10/40, Drug: atorvastatin 20 mgParticipants received 20 mg open-label atorvastatin during a 5-week run-in period. Following this run-in period, ezetimibe/simvastatin 10/40 was administered once daily in tablet form during the 6-week double-blind treatment period
atorvastatin 40 mg	Active comparator	Drug: atorvastatin 40 mg, Drug: atorvastatin 20 mgParticipants received 20 mg open-label atorvastatin during a 5-week run-in period. Following this run-in period, 40 mg atorvastatin was administered once daily in tablet form during the 6-week double-blind treatment period

Who may qualify

Ages: 18 to 79 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Participants who are either statin naive or on approved lipid lowering therapy for 6 weeks prior to study initiation
Participant meets Adult Treatment Panel (ATP) III High Risk criteria

Key exclusion criteria (8 listed)

Females who are pregnant or breastfeeding
Participant consumes more than 14 alcoholic beverages per week
Participant has been treated with an investigational drug within the last 30 days
Participant has congestive heart failure (New York Heart Association [NYHA] Type III or IV)
Participant has had gastric bypass

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
ezetimibe/simvastatin 10/40Also: Vytorinezetimibe/simvastatin 10/40 tablet once daily for 6 weeks.	Drug	ezetimibe/simvastatin 10/40
atorvastatin 40 mgAlso: Lipitoratorvastatin 40 mg tablet once daily for 6 weeks	Drug	atorvastatin 40 mg
atorvastatin 20 mgAlso: LipitorAll participants will take atorvastatin 20 mg tablet once daily for the 5 week run-in period before randomization	Drug	atorvastatin 40 mg, ezetimibe/simvastatin 10/40

Primary outcome

Percent Change From Baseline in Low Density Lipoprotein (LDL)-C
Time frame: Baseline (Treatment Day 1), Treatment Week 6

14 secondary outcomes

Number of Participants Reaching LDL-C Target Goals of <70 mg/dL
Time frame: Treatment Week 6
Number of Participants Reaching LDL-C Target Goal <77 mg/dL
Time frame: Treatment Week 6
Number of Participants Reaching LDL-C Target Goal <100 mg/dL
Time frame: Treatment Week 6
Percent Change From Baseline in Total Cholesterol
Time frame: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Triglycerides
Time frame: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol
Time frame: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Non-HDL Cholesterol
Time frame: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in LDL-Cholesterol/HDL-Cholesterol Ratio
Time frame: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Total Cholesterol/HDL-Cholesterol Ratio
Time frame: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Non-HDL Cholesterol/HDL-Cholesterol Ratio
Time frame: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Apolipoprotein B
Time frame: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Apolipoprotein A-1
Time frame: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in Apolipoprotein B/A-1 Ratio
Time frame: Baseline (Treatment Day 1), Treatment Week 6
Percent Change From Baseline in High-sensitivity C-Reactive Protein (Hs-CRP)
Time frame: Baseline (Treatment Day 1), Treatment Week 6

Results and safety

Results posted to the registry on 31 Oct 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ezetimibe/Simvastatin 10/40	120	116
Atorvastatin 40 mg	130	125

Primary outcome: Percent Change From Baseline in Low Density Lipoprotein (LDL)-C

Time frame: Baseline (Treatment Day 1), Treatment Week 6. Least squares mean (95% Confidence Interval). Unit: percent change from baseline

Measure	Ezetimibe/Simvastatin 10/40 n = 117	Atorvastatin 40 mg n = 126
Value	-26.81 (27.09)	-11.81 (22.85)

Ezetimibe/Simvastatin 10/40 vs Atorvastatin 40 mg: Difference in Least Squares Means: -15.00 (95% CI -21.15 to -8.84), p <0.001, Longitudinal Data Analysis (LDA) Model

Population analysed: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with percent change data available at week 6.

14 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5.0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ezetimibe/Simvastatin 10/40	1 of 119 (0.8%)	0 of 119 (0%)	Not reported
Atorvastatin 40 mg	1 of 130 (0.8%)	2 of 130 (1.5%)	Not reported
Placebo	0 of 1 (0%)	1 of 1 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22293030Hing Ling PK, Civeira F, Dan AG, Hanson ME, Massaad R, De Tilleghem Cle B, Milardo C, Triscari J. Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study. Lipids Health Dis. 2012 Jan 31;11:18. doi: 10.1186/1476-511X-11-18.
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 Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ezetimibe/simvastatin 10/40, atorvastatin 40 mg and atorvastatin 20 mg 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 2 inclusion and 8 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 16 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?

Yes. Results are posted in the registry (first posted 31 Oct 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percent Change From Baseline in Low Density Lipoprotein (LDL)-C (time frame: Baseline (Treatment Day 1), Treatment Week 6). 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 NCT00782184, 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 16 May 2024.